Formulation Approaches for Solubility Enhancement by Using Polar or Non-Polar Lipid Components of BCS Class II Drugs through LBDDS
Aditya Sharma1*, Vaibhav Rastogi2, Prevesh Kumar2, Neelkant Prasad3
1School of Pharmaceutical Sciences, IFTM University, Moradabad-244102, Uttar Pradesh, India.
2Pharmacy Academy, IFTM University, Moradabad-244102, Uttar Pradesh, India.
3SGT College of Pharmacy, SGT University, Gurugram-122505, Haryana, India.
*Corresponding Author E-mail: adi99463@gmail.com
ABSTRACT:
At present, Lipid based preparations such as self-emulsifying, self-microemulsifying and self-nanoemulsifying drug delivery systems are reconnaissance in various treatment as a powerful methodology for improving the biocompatibility, bioavailability and disintegration pace of Biopharmaceutics Classification System Class II drugs. These details manages various preferences likewise decrease in food impact and between individual abnormality, effectiveness of preparations and the likelihood of assembling utilizing basic excipients realistic in the market. These preparations are essentially produced and physically unchangeable blends of oil, surfactants, co-surfactants and solubilized drugs that may regulated orally. These arrangements may also a financially conceivable approaches to articulate various pharmaceutically appropriate dosage forms with respect to topical, oral, pulmonary, or parenteral distribution. Present studies recommend a taxonomic outline of lipid-based systems and their mechanisms required to extend the dissolvability and bioavailability of inadequately water soluble drugs as like Aceclofenac, Gliclazide, Glibenclamide, Glimipride, Ketoconazole and so forth. Few constituents of lipid-based distribution can be used like Soya lecithin, Olive oil, Soyabean oil, Poloxomer, Tween 80 etc. specifically for oral delivery because of their physicochemical and biopharmaceutical viewpoints with their real effective characteristics. Additionally, this review also emphases about the methods can be utilized to get ready such conveyance delivery systems.
KEYWORDS: Self-emulsifying drug delivery systems; Self-micro emulsifying drug delivery systems; Self-nano emulsifying drug delivery systems; Biopharmaceutics Classification System; Bioavailability; Gliclazide; Soya Lecithin; Soyabean oil.
INTRODUCTION:
Jw = PwCw
where, Jw is the drug flux through the intestinal wall at any position and time, Pw is the permeability of the membrane, and Cw is the drug concentration at the intestinal membrane surface.
According to BCS, the drugs have been discriminated based on their solvency and porousness [4] and are ordered into four Classes, for example Class I drugs having high solubility and high permeability, Class II drugs having low solubility and high permeability, Class III drugs having high solubility and low permeability and Class IV drugs having low solubility and low permeability. [4-8] The BCS has been considered to be a helpful device for basic leadership in the revelation and early improvement of new drugs. BCS direction expands the administrative application of the BCS and recommends the strategies for classifying drugs. It likewise clarifies when a waiver for in-vivo BA and bioequivalence (BE) studies might be mentioned dependent on the methodology of BCS. [1]
It grants for the extrapolation of in-vivo pharmacokinetics of oral immediate-release (IR) drug products by listing the drug compounds into four classes founded on their solubility associated to dose and intestinal permeability in blend with the dissolution properties of the dosage form. [5,9] BCS guidance was provided by USFDA, to improve the efficiency of drug product development process. [10] Objectives of BCS are-
1. To improve the effectiveness of the medication advancement and audit process by prescribing a system for recognizing extra clinical BE test.
2. To prescribe a class of IR strong oral measurements structures for which BE might be surveyed dependent on in-vitro disintegration tests.
3. To prescribe techniques for arrangement as per measurements structure disintegration alongside the dissolvability penetrability qualities of the drug dose.
The in-vivo show of orally controlled medications relies on their dissolvability and tissue porousness attributes. The release rate or solvency of the drug substance won't be an considerable factor if the retention of the drug is penetration rate restricted and in such cases the in-vitro dissolution study can be utilized to make apparent the BA or BE of the medication item through in-vitro/in-vivo relationship (IVIVC).
On the other hand if absorption of the drug is dissolution rate limited that means the drug in the gastrointestinal (GI) fluid permits freely through the bio-membranes at a rate higher than it dissolves or is released from the dosage form. The specifically deliberated in-vivo study will be required in such a case, to access the absorption rate, and hence it’s BA and to demonstrate the BE ultimately. Such a drug substance is a good candidate for controlled delivery provided be suitable in terms of their pharmacokinetics and pharmacodynamics for well-ordered release improvement.
Then again if ingestion of the drug is dissolution rate constrained that implies the drug in the gastrointestinal (GI) liquid allows unreservedly through the bio-layers at a rate higher than it breaks up or is released. The explicitly deliberated in-vivo study will be required in such a case, to get to the GI retention rate, and consequently its BA and to show the BE eventually. Such a drug substance is a decent contender for controlled conveyance gave be appropriate as far as their pharmacokinetics and pharmacodynamics for well-requested release enhancement.
Additionally if a drug itself is having low dissolvability and a moderate dissolution rate, the release will consequently get increasingly slow and formulation need not have an in-built release obstruction component, rather the assimilation will presently be represented by the gastric purging rate. Along these lines, the dose structure must most likely control inside the ingestion window for an adequate time with the goal that assimilation can occur. In such case, a hydro-dynamically balanced (floating) system or a mucoadhesive dose structure will fill the need.
These classification expand the regulatory applications of the BCS and authorizes methods for classifying the drugs based on their solubility and permeability. Henceforth, the BCS can graft as management tool for the formulation and development of numerous drug delivery system methodologies. [11]
Compounds with poor solubility have been well-considered to confront noteworthy solubilization obstructions and are viewed as for all intents and purposes insoluble drugs as indicated by different official compendia. The new drug objects with poor water solvency are ending up increasingly common as consequence of high-throughput determination in drug discovery. Poorly water soluble (PWS) drugs offers major difficulties, as it decreases the oral absorption and BA. All things considered, the expected dissolvability to accomplish a decent solvency and BA basic to be assessed in appraisal of both the portion of medication just as the penetrability. [12-14]
Dissolvability, dose and permeability in BCS which groups PWS drugs as Class II and Class IV are additionally the key hidden factors. Drug materials are well thought-out as highly dissolvable, if the biggest strength is in credit to ≤250 ml over the physiological pH ranging from 1.0 to 7.8. Or something might happen, the drug substance is viewed as inadequately soluble. The exceedingly penetrable drugs are characterized as those aggravates that display more noteworthy than 90% ingestion of the regular dose. Something else, the medication substance is estimated to be inadequately permeable. [15-20]
Solvency or permeability both are likely to constrain the oral absorption of drugs in GI tract. Herein, the drug retention is studies as dissolution rate-constrained if the particles can't break down totally during the change time to the assimilation site, whereby expanding the portion as well as lessening molecule size to sub-micron range should upgrade the ingestion. [21] Likewise, if the quantity of fluid accessible in GI tract isn't sufficient to break up the managed portion, the dissolvability turns into the rate limiting step in absorption. [22] For the situation of permeability-limited absorption, the change pace of the drug over the gut divider is delayed for the length of the living arrangement time in the retention site. [23]
From above discussion it is obvious that absorption and BA of the Class II drugs are dissolution rate limited. Therefore, on the way to improve their absorption and BA, their solubility and hence dissolution rate must be improved.
FORMULATION APPROACHES FOR SOLUBILITY ENHANCEMENT:
Various formulation approaches available for dissolution rate enhancement are given by various researchers are discussed in the following sections-
1. Solid Dispersion:
Solid dispersion (SD) is a methodology to handle solubility/ dissolution rate restricted of oral retention by dispersion for at least one active ingredients in an inactive transporter at the solid state. SDs may expand disintegration rate or potentially solvency by diminishing molecule size, improving wettability, diminishing agglomeration, modifying physical condition of the medication and perhaps dispersion on a molecular level. [24]
A truly steady SD is accomplished if the drug is dispersed as precious crystels in the indistinct polymer stage since the drug stays in its favored crystalline state. A metastable SD is acquired if the drug substance is changed into its indistinct state yet not molecular dispersed in the shapeless amorphous polymer stage since the drug may recrystallized during capacity or preparing. Both those kinds of SD are called glass suspension. [25]
Molecular dispersion speaks to a definitive in molecule size decrease and after the bearer has disintegrated, the drugs are available as a supersaturated arrangement. The ability of drug to keep up broke up in the supersaturated arrangement is unequivocally relies upon the polymer attributes. [26]
It additionally included arrangement of eutectic blends of drugs with water-solvent bearers by liquefying of their physical blends, and once the transporters broke down, the medication accelerated in a finely isolated state in water. [26]
Distinctively, the solvency of a drugs in a polymer is well-considered to be beneath 10%, consequently a metastable SD is as often as possible gotten if the drug is changed into its indistinct state. In such a framework the nebulous drugs tends to secret back to its comparing crystalline structure. [24, 26]
Other important properties for the carriers those are considered to be important for preparation of SDs include enough thermal stability, thermoplasticity, solubilizing properties, and for the SD systems prepared by hot extrusion technique; and high solubility in organic solvents for the systems manufactured by the solvent method. [24]
SD increase solubility, dissolution rate, and hence BA by resulting in reduced particle size and thus improved specific surface area. [24]
The transporter used in the SD also plays a vital role in improving the wettability of the particles. Enhanced wettability offers to increase in solubility thus improve the BA. [27-29]
In SD drugs are accessible as supersaturated solutions which are well thought-out to be metastable polymorphic stage. Thus offering the drug in amorphous form and increases the solubility of the drug particles. [29, 30]
In contrast, the major disadvantages of SD such as their instability, changes in crystallinity and decrease in dissolution rate with ageing, temperature and moisture have more deteriorating effect on SDs than on physical blends. These are also difficult to handle at the time of preparation of formulation because of tackiness. [31]
2. Complexation with cyclodextrins:
Complexation is one of a few different ways to emphatically improve the physicochemical properties of pharmaceuticals. It might gently be characterized as the reversible relationship of a substrate and ligand to frame another species. [32] Although the order of buildings is fairly discretionary, the separation is typically founded on the sorts of collaborations and species included, e.g., inclusion complexes, molecular complexes, metal complexes and ion-exchange compounds. Cyclodextrins (CDs) are regular instances of intensifies that structure consideration edifices. These buildings are framed when a "visitor" atom (sedate) is somewhat or completely included inside a "host" particle for example CDs with non-covalent holding. At the point when consideration buildings are shaped, the physicochemical parameters of the guest molecule are camouflaged or changed and upgrades in the particle's taste, dissolvability, steadiness, wellbeing, BA, and so forth are generally observed. Impediments in the pharmaceutical utility of the CDs were winding up surely understood and derivatives were set up with the point of improving attributes, for example, complexing ability, dissolvability, and security. [33]
Scientific articles have perceived the research applications for CDs, though the licenses have demonstrated an expanding enthusiasm for the business insurance of CDs in pharmaceutical items. By and by, the normal utilization of CDs in plans is still questioned. The hesitance to improve a CDs formulations is fundamentally because of the dubious administrative receipt of a plan containing an unusual inactive component. [32]
Numerous advantages of inclusion complexation have been accounted for example, improved solvency, upgraded BA, better stability, taste and smell covering additionally decreased unpredictability, and modified drug release. [34]
The drawbacks of this technique included relentless and reproducibility of physicochemical qualities, scale-up of manufacturing process, trouble in joining into definition of drug delivery, costly strategies for preparation, stability issues and practicability of complexation of just little portion drugs. [35]
3. Polymeric micelles:
Consequently, Polymeric micelles (PMs) being proposed as conceivable drugs bearers just because by Bader in 1984 [36] and have created as potential carriers for PWS drugs by solubilizing them in their internal core and present appealing features, for example, a for the most part little size i.e. 100 nm and tend to avoid searching by the mononuclear phagocyte systems. [37] PMs are the systems with diameter lesser than 100 nm formed by amphiphilic polymers scattered in an aqueous media, and characterized by a center shell structure which may have the hydrophilic polymer shell and the hydrophobic polymer center or an A-B-A multi-square structure of co-polymers of various hydrophobicity or a join co-polymer. [37, 38] Accordingly, PMs have the hydrophobic pieces structure at the center of the micelle, while hydrophilic sections structure in the micelle's crown. The nonpolar atoms are solubilized inside the hydrophobic center while polar particles will be adsorbed on the micelle surface and the substances with halfway extremity will be appropriated along surfactant particles in moderate positions. [39] Block co-polymer micelles are additionally grouped based on intermolecular powers driving the isolation of the center section from the aqueous condition, for example, amphiphilic micelles (framed by hydrophobic connections), poly-particle complex micelles (coming about because of electrostatic collaborations) and micelles beginning from metal complexation and forming chains may result in various non-spherical structures including rods and lamellae. [40]
In general, there are two foremost different procedures for drug- stacking into the PMs, the main first procedure is the immediate disintegration technique and the subsequent procedure is the planning of drug-loaded micelles by solvent expulsion. [38, 40] The immediate disintegration technique is a basic strategy, generally utilized for mindfully hydrophobic co-polymers. It comprise of dissolving the block copolymers alongside the drugs in a aqueous solvent, which may expect warming to actuate micellization. The second class of drug-loading technique is connected for amphiphilic co-polymers which are not promptly dissolvable in water and require a natural dissolvable basic to both the copolymer and the drug.
Micelle formation relies on the dissolvable evacuation strategy which can be one among the few strategies like dialysis, oil-in-water emulsion technique [37], solution casting [40] and freeze-drying. [41] Thus, PMs have various favorable circumstances as drug bearers and can join a few inadequately dissolvable drugs and are viewed as steady, sheltered and cheap drug transporters. Micelle encapsulated drug have the option to focused the organs or tissues of intrigue which can be accomplished through the improved penetrability and maintenance impact. Site specific focusing of PMs is conceivable by setting up the thermal or pH delicate block co-polymers and furthermore, a vector atom like saccharide, hormone, counter acting agent, peptide, lectin, and some low-sub-atomic weight mixes can be joined to the outside of micelles that help with focusing against explicit ligands at explicit site of interest. [38]
PMs are special drug carrier systems that not just improve water solvency of numerous hydrophobic drugs, yet in addition are pertinent to drug focusing, formulating unstable drugs and diminishing the unfavorable impacts. Because of their across the board applicability to huge gathering of therapeutic mixtures, drug stacking into PMs is a propitious molecule strategy to detail other inadequately dissolvable drugs later on. [41]
The foremost benefits of PMs Drug carrier technique is its high water dissolvability even though consolidates a lot of hydrophobic.[42] Mostly, in traditional synthetic polymer-drug conjugate systems and antibody-drug conjugate systems, loss of the carrier’s water solubility subsequent from the conjugation of a hydrophobic drug produces a severe issue. In excess of a couple of research gatherings detailed this issue of the polymer-sedate conjugates in blends [43-45] and in their intravenous infusions PMs can fuse an enormous number of hydrophobic drug particles in the micelles at internal core, and all the while, the micelles can keep up their water solvency by restraining intermicellar collection of the hydrophobic cores with a hydrophilic external shell layer that fills in as a boundary against intermicellar conglomeration. This is an incredible preferred advantage in light of the fact that numerous powerful drugs that have been created as of late are exceptionally hydrophobic and are, in this manner, water insoluble. Above foremost part, polymeric surfactants delivers less toxic quality than low-atomic-weight surfactants, similar to sodium dodecyl sulfate. [44] Principally, PMs are viewed as safe in connection to endless toxic quality. [43-45] Numerous varieties chemical substances can be combined into PMs, additionally hydrophobic interactions similarly work as a driving force for micelle advancement. [44]
The principal drawback of PMs is reality that generally abnormal amounts of polymer science are required in PMs Studies. The second inconvenience for the PMs Systems is the undeveloped innovation for drug incorporation in a physical way. [42] This was also reported that physical combination efficiencies were subject to different factors in drug-incorporation processes. [42] Presently, there appear to be no general consolidation technique pertinent to any polymer. Besides, in certain strategies the medication fuse might be hazardous on an enormous modern scale, while the drug incorporation is simple and effective little research facility scale. [45] The third disadvantage is far slow extravasation of polymeric bearer frameworks than that of low-sub-atomic weight drugs. [41] This outcomes from a distinction in extravasation instruments between polymeric carrier systems and low sub-atomic weight drugs. [41] The polymeric systems translocate from the blood circular system to the interstitial space of organs and tissues through intra-cell channels and between cell intersections, while the drugs pervade legitimately finished and finished with lipid bilayer cell layers. In this way, a protracted flow character of the PMs is a basic prerequisite for conveyance of a helpful sum attributable to repayment of the moderate extravasation with a huge territory under the bend esteem that outcomes from the long pivot. The drawback is a danger of unending liver harmfulness. [42] Subsequently, harmful reactions of the conjugated and consolidated medication might be displayed for a more drawn out period than an instance of free drugs whose lethal properties can be brought down through digestion in a brief period. [42]
4. Particle size reduction:
The inherent BA is identified with drug molecule size. By diminishing molecule size, expanded surface zone improves the disintegration properties. [46] The reduction of drug particle size is finished by processing methods utilizing plane plant, rotor stator colloid factories and so forth. This technique isn't reasonable for drugs having a high portion number since it doesn't change the immersion dissolvability of the drugs. Molecule size reduction should be possible by micronization and nano suspension. Every system uses various types of gear for decrease of the molecule size. [46]
In micronization, the dissolvability of drug is frequently in a general sense identified with drug molecule size. Micronization of drugs are finished by processing methods utilizing roller mills, jet mill, ball mills, rotor-stator colloid mills, crusher mills and so on. Micronization isn't appropriate for drugs having a high portion number since it doesn't change the immersion solvency of the drugs. [46] One more technique is Nano suspension in which presents sub-micron colloidal dispersion of pure particles of drug, which are stabilized by surfactants. The nanosuspension approach has been employed for drugs including Amphotericin B, Paclitaxel, Tarazepide, Atovaquone and Bupravaquon. [46]
One more strategy is Nano suspension in which presents sub-micron colloidal dispersion of unadulterated particles of drugs, which are balanced out by surfactants. The nanosuspension approach has been utilized for drugs including Tarazepide, Paclitaxel, Amphotericin B, Bupravaquon and Atovaquone.
The favorable circumstances offered by nanosuspension are expanded disintegration rate because of bigger surface zone exposed, while deficiency of ostwald aging is because of uniform and thin molecule size range acquired, which takes out the focus slope factor. Nanosuspensions are made by homogenization and wet milling process.[46]
Benefits of particle size reduction method are solubility enhancement include quick development of liquid forms for pre-clinical stage testing that be able to change into solids for future clinical development and also deals with low excipient to drug ratios, well tolerated formulations provided in case that strong surfactants are not necessary for stabilization, and the method for combinations that defeat prior hard work to rise up the solubility. [46]
Then again, impediments of this technique incorporate a solid propensity for molecule agglomeration because of high surface charge on discrete small particles. Further, growing up a strong measurement structure with a significant salary load without empowering agglomeration might be in fact testing. Additionally, advancement of clean intravenous details is much all the more testing. [46]
5. Cryogenic Techniques:
Cryogenic techniques have been created to improve the dissolution pace of drugs by making nanostructured amorphous drug particles with high level of porosity at extremely low temperature conditions. Cryogenic creations can be characterized by the sort of infusion gadget (fine, rotating, pneumatic, and ultrasonic spout), area of spout (above or under the fluid level), and the structure of cryogenic fluid (hydrofluoroalkanes, N2, Ar, O2, and natural solvents). After cryogenic handling, dry powder can be acquired by different drying procedures like splash stop drying, air stop drying, vacuum stop drying, and lyophilisation. [47-49]
Briggs and Maxvell [50] concocted the procedure of spray freezing onto cryogenic liquids. In this method, the drugs bearer like inositol, maltose, mannitol, lactose, or dextran etc. were disintegrated in water and atomized over the outside of a bubbling fomented fluorocarbon refrigerant. Sonication test can be put in the blended refrigerant to upgrade the dispersion of the fluid arrangement. [50]
An additional technique is spray freezing into cryogenic liquids (SFL). It is a molecule designing technology has been utilized to create nebulous nanostructured totals of drug powder with high surface zone and great wettability. It fuses direct fluid impingement between the automatized feed arrangement and cryogenic fluid to give extraordinary atomization into miniaturized scale beads and thusly altogether quicker solidifying rates. The solidified particles are then lyophilized to acquire dry and free-streaming micronized powders. [51, 52]
One more further technique is ultra-rapid freezing (URF) which is a novel cryogenic innovation that makes nanostructured drug particles with significantly upgraded surface zone and wanted surface morphology by utilizing strong cryogenic substances. Use of drug solutions for the strong surface of cryogenic substrate prompts momentary solidifying and resulting lyophilization (for expulsion of dissolvable) structures micronized drug powder with improved solvency. Ultra quick solidifying freezing hinders the stage partition and the crystallization of the pharmaceutical ingredients prompting personally blended, formless drug transporter SDs, and strong arrangements of solutions. [53]
6. Hydrotrophy:
Hydrotrophy is a solubilization technique, whereby expansion of a lot of second solute for example the hydrotropic agent, increments in fluid dissolvability of initial one. These hydrotropic specialists are ionic natural salts which comprises of soluble base metal salts of different natural acids. Added substances or salts that increases dissolvability in given dissolvable are said to be "salt in" the solute and those salts that diminishes the solvency are said to be "salt out". A few salts contains huge anions or cations that they themselves are extremely soluble in water bring about "salting in" of nonelectrolytes called "hydrotropic salts" and a phenomenon known as "hydrotropism." Hydrotrophy technique is plan to raise the dissolvability in water because of the nearness of enormous amount of added substances. The component by which it upgrade the dissolvability is all the more intently related to complexation including a frail communication between the hydrotrophic operators like sodium acetic acid derivation, sodium alginate, sodium benzoate, urea, and the ineffectively solvent drugs. [54, 55] The hydrotropes are known to self-collect in solution. The arrangement of hydrotropes is difficult based on atomic structure, since a wide assortment of mixtures have been accounted for to display hydrotropic behavior. Explicit models may incorporate sweet-smelling alcohols like resorcinol, pyrogallol, ethanol, catechol, α and β-naphthols and salicylates; ionic surfactants like diacids and sodium dodecyl sulfate; and alkaloids like caffeine and nicotine. [56]
Hydrotropes with cationic hydrophilic group are uncommon, for instance salts of fragrant amines, for example, procaine hydrochloride. Also improving the solubilization of mixes in water, they are consented to show the impacts on surfactant total prompting obfuscating of surfactants, development of micelle, stage indication of multicomponent frameworks with reference to nanodispersions conductance permeation, polymers, etc. [57]
7. Crystal Engineering:
In this method, the surface area of drug molecule accessible for disintegration is reliant on its molecule size and capacity to be wetted by luminal liquids. This molecule size, which is basic to sedate disintegration rate, is subject to the states of crystallization or on methodologies of comminution, for example, impact milling and fluid energy milling. This comminution strategies can deliver those particles which are incredibly heterogeneous, charged, and strong, with the possibility to cause issues in downstream preparing and item execution. Thus crystal engineering techniques are built up for the controlled crystallization of drugs to yield high virtue powders with well-characterized molecule size dispersion, surface nature, surface vitality, crystal habit and crystal form (crystalline or amorphous). [58]
Consequently, polymorphs for a similar drug may change in their physicochemical properties, for example, dissolvability, stability, liquefying point, and disintegration rate. The vast majority of the drugs show basic polymorphism and it is attractive to build up the most thermodynamically stable polymorph of the drug to convince reproducible BA of the item over its time duration of usability under a scope of real-world conditions. A standard case of the significance of polymorphism on BA is that of chloramphenicol palmitate suspensions, demonstrated the steady polymorph of chloramphenicol palmitate, yield low serum levels, while the metastable polymorph chloramphenicol palmitate delivered a lot higher serum levels when a similar portion was coordinated to oversee. [59]
Crystal engineering technique likewise includes the planning of hydrates and solvates for expanding the disintegration rate. All through the crystallization procedure, it is conceivable to trap particles of the dissolvable inside the cross section. On the off chance that the dissolvable utilized is water, the resultant precious crystal is a hydrate; if some other dissolvable is utilized, it is alluded to as solvate. The disintegration rate and dissolvability of a drug can vary essentially for various solvates. For instance, glibenclamide has been disengaged as pentanol and toluene solvates, and these solvates indicated higher solvency and disintegration rate than two nonsolvated polymorphs. [60] It is feasible for the hydrates to have a quicker or slow disintegration rate than the anhydrous structure. The most typical circumstance is for the anhydrous structure to have a quicker disintegration rate than the hydrate. For instance, the disintegration pace of theophylline anhydrate was quick than its hydrate structure. [61]
In some specific cases, hydrate type of the drug may indicate quick disintegration rate than its anhydrous structure. Erythromycin dihydrate was found to show real differences in the disintegration rate when differences with monohydrate and anhydrate structures. [62]
Pharmaceutical cocrystals demonstrates another way to address the issues of inadequately solvent drugs. [63] Pharmaceutical cocrystals are set up by delicate vanishing from a drug particle arrangement containing stoichiometric measures of the parts (cocrystal formers); be that as it may, sublimation, development from the liquefaction, or crushing of at least two strong cocrystal formers in a ball factory are likewise fitting similarly. [64] Carbamazepine: saccharin cocrystal was presented to be predominant crystal types of carbamazepine alone as far as disintegration, stability and suspension. [65] Customary crystallization strategies incorporate sublimation, crystallization from arrangements, vanishing, desolation, or crushing. All these methods are being supplanted with the different strategies for precious Crystal enginnering, such as the super critical fluid (SCF) technologies [66, 67] to yield pharmaceutical solids with wanted dissolvability, disintegration rate and stability.
A different developing technique is melt sono-crystallization that take ultrasonic vitality to deliver permeable fast dissolving particles for hydrophobic molecules of drug. Based on these thrilling reports, liquefy sono-crystallization plays out the precious crystal designing strategies should be misused more for upgrading the disintegration pace of PWS drugs. [68]
8. Co-solvency:
PWS drugs dissolvability can be expanded as often as possible by the expansion of a water miscible solvent in which the drug has higher dissolvability known as co-solvents. [69] Co-solvents are blends of water miscible solvents used to deliver an answer with improved dissolvability for PWS mixes. Generally, this is one of the most broadly utilized methods since it is easy to create and assess co-dissolvability has been used in various details including solids and fluids. Instances of solvents utilized in co-dissolvable blends are propylene glycol, PEG 300 or ethanol. Co-dissolvable details of PWS drugs can be managed through oral and parenteral route. It might need to expansion of water or weakening with a watery medium to bring down the dissolvable fixation at the season of preceding organization of drugs. [70] Co-solvents can expand the dissolvability of inadequately solvent mixes at a few thousand times contrasted with the watery solvency of the medication as it were. Higher medication groupings of ineffectively solvent mixes can be broken up contrasted with other solubilization draws near. [70-72]
Seedher and Bhatia [73] examined that the aqueous dissolvability of Rofecoxib, Celecoxib and Nimesulide could be upgraded altogether by utilizing ethanol as the subsequent dissolvable and PEG-400-ethanol had most solubilization possibility among the mix dissolvable systems. In any case, the BA may not be drastically expanded on the grounds that the PWS drugs will commonly crash out upon weakening into a crystalline or amorphous precipitate. For this situation, disintegration of this amorphous precipitate is required for oral integration. [73-75] Co-solvents might be joined with other solubilization procedures and pH change in accordance with further increment dissolvability of ineffectively dissolvable mixes. These days, dimethyl sulfoxide and dimethyl acetoamide have been generally utilized in this system as co-solvents in view of their enormous solubilization limit with regards to ineffectively dissolvable medications and their moderately less toxicity. [76-79]
9. Lipid based formulations:
Nowdays, a lot of intrigue has been focussed on lipid based carrier systems. The most well-known methodology is the fusion of the dynamic PWS segment into idle lipid vehicles, for example, oils, surfactant dispersions [80], SDs, solid lipid nanoparticles, emulsions [80], micro emulsions [81], micro/ nano emulsifying formulations [81], nano emulsions [82], self-emulsifying formulations (SEF), liposomes [82], niosomes [83] etc.
Lipid based preparations for oral administration of drugs are an assorted group of preparations having a wide scope of properties. The convenience of solubilizing lipid-based preparations for improving the GI ingestion of PWS and hydrophobic drugs are very much reported in the literature. These for the most part comprise of a drugs that disintegrated in a mix of excipients with wide assortment of physicochemical properties running from unadulterated triglyceride oils, mono and diglycerides, and significant extent of lipophilic or hydrophilic surfactants and cosolvents. [84]
The essential activity, by which a lipid preparation prompts improved BA is generally evasion of the moderate disintegration process which constrains the BA of hydrophobic drugs from solid dosage structures. Ideally the preparations enables the drugs to stay in a broke down state all through its transit in the GIT. The drug for ingestion can be improved by preparation of the drugs as a solubilizate inside a colloidal dispersion. This target can be accomplished by preparations of the drugs in a self-emulsifying systems. Among different methodologies, self-emulsification of drug conveyance systems has increased more consideration because of improved oral BA empowering decrease in doses, progressively reliable profiles of drug ingestion, particular focusing of drugs toward explicit retention window in GIT, and assurance of drugs from the threatening condition in gut. [81]
Several lipid-based drug delivery systems (LBDDS) consist of self-emulsifying, self-micro emulsifying, and self-nano emulsifying drug delivery system (SEDDS, SMEDDS, and SNEDDS respectively). These are physically steady isotropic blends of oil, surfactant, and co-surfactant that quickly and suddenly structure form oil in water emulsions, smaller scale emulsions, or nano emulsions separately, when brought into fluid stages under delicate disturbance. [81] Therefore, self-emulsifying preparations are promptly dispersed in the GIT, where the motility of the stomach and small digestive system gives the fomentation important to emulsification.
The prospective preferences of SEDDs incorporate 100% drug ensnarement limit, physically stable preparations, no disintegration step required, arrangement of submicron globules size, along these lines expanding assimilation surface region, increment in rate and degree of retention, and in this way expanded BA. [84, 85]
SEDDS convey BCS Class II drugs adequately. SEDDS have potential for viable conveyance of BCS Class III, BCS Class IV and hydrolytically prone drugs. They give insurance against gastric corruption and reliable transient profile with decreased dosing and dosing recurrence. These are anything but difficult to make and scale-up. It likewise coordinates the dispersion of drugs into the lymphatic systems. [84] SEDDS have been depicted as the systems that produce emulsions with a globule size somewhere in the range of 100 and 300 nm while SMEDDS structure straightforward miniaturized scale emulsions with a globules size of under 50 nm. [85] Still, SEDDS usually states to a wide range of emulsifying systems except if generally portrayed, while SNEDDS depict systems which structure nano emulsions upon dispersion in fluid media. [86]
Being anhydrous, these systems also offer a great potential for the formulation and administration of hydrolytically susceptible drugs. SEDDS are also found to increase the intestinal permeability and minimize the effect of pH on drug absorption. [87]
While the essential component by which these details are thought to improve drug retention is through end of the requirement for pre-absorptive drug solubilization in the GIT. [88, 89] Other components may incorporate protection from substance and enzymatic debasement limited in the watery condition of the GIT and advancement of lymphatic drugs transport, which dodges hepatic first-pass metabolism. [88, 89]
LBDDS are chosen for solubility enhancement because of much interest as carriers for the delivery of drugs with poor water solubility as lipids are amphiphilic in nature and thus, these can carry a wide range and all class of drug. Though lipids are costly, their obvious advantages like biodegradability, non-toxicity, their positive health effects in hyperlipidemia as hypercholesterolemia and their various nutritional benefits commence by the researchers to avoid the economic disadvantages. [90]
Advantages of LBDDS are that these are structurally most close to natural biological membrane lipids. The BA of certain drugs are improved when co-administered with fatty/ lipid ingredients. [90-92] Further, lipids and lipid formulations are biodegradable and biocompatible, and also have viabilities of carrying both lipophilic and hydrophilic drugs, and have low risk profile. [90-92]
The distinctive characteristics of lipids viz., their biocompatibility, physiochemical diversity and confirmed capability to improve oral BA of PWS or lipophilic drugs through discriminatory lymphatic uptake have make them much attractive carriers for oral preparations. [90, 91]
Other lipid based formulations available are liposomes [82], niosomes [83], emulsions [80], micro-emulsions [81] etc. But SEDDS have been opted for research project as the former methods involve complex technologies in processing. [86, 87]
SEDDS are composed of two types of components. First is surfactant mix containing polar lipid/s and a non-ionic surfactant, and the other is non-polar lipid. [93, 94]Soya lecithin can be used as a polar lipid. Lecithin has been a prominent enhancement since it's high choline content. Choline is a basic supplement that has advantage for heart wellbeing and mental health, as choline inadequacy assumes a job in liver sickness, atherosclerosis, and conceivably neurological issue. It is especially significant for pregnant ladies to get enough choline, since low choline admission may raise the pace of neural cylinder abandons in newborn children, and may influence their child's memory. [95] Fats and oils are neutral mixtures. When one of the unsaturated fats in a triglyceride is supplanted by a phosphate group, a phospholipid is acquired that has two nonpolar hydrophobic tails and a charged hydrophilic head.
Polyoxyethylene, Polysorbates (Tween™), castor oil, glycerol monohydroxystearate and Sorbitan monopalmitate may be used as another component of surfactant mix as it is non-toxic in nature. It is also considerable to meet the solubility requirements. [95, 96]
As far as non-polar component is concerned we had option of cholesterol (component of niosomes and liposomes), fatty acids, fatty alcohols, poly ethylene glycol etc. [88] Cholesterol, fatty acids and fatty alcohols are avoided for their negative health effects like that on the blood lipid profile, including elevation of LDL cholesterol, a well-accepted biomarker for risk of cardio vascular disease. [88, 89]
CONCLUSION:
BCS Class II drugs have been on attention for solubility enhancement researches and more than a few formulation approaches for this class of compounds have been established. Different strategies those have been actualized by different analysts like comelt dispersion, coprecipitation with hydrsophilic polymers, hydrotrophic procedures, molecule estimate decrease, gem building methods, strong scattering, incorporation complexation, micellization, cryogenic systems, emulsification, drug lipid carriers and self-emulsifying drug delivery systems and so forth. Every one of these procedures have their own points of interest and impediments. Poor fluid dissolvability of a BCS Class II drug can be tended with particulate drug delivery systems innovations. The same number of drugs are as of now propelled in the market effectively as lipid-based plans, the LBDDS has a wide range in compatibilities of dissolvability and BA upgrade. This audit concentrated on the present patterns in the field of LBDDS as for plan approaches and their portrayal. In LBDDS, particulate drug delivery systems have been of most consideration in light of the fact that these have bigger explicit surface zone for disintegration than different kinds of plans. An increasingly uniform drug discharge can likewise be accomplished from these plans by creating the definition of uniform molecule estimate. Among particulate drug delivery systems lipid plans are of most status since lipids are amphiphillic in nature that makes them reasonable for conveying a wide scope of drug from each class. Lipids likewise look like bilayered organic film structure that causes its simple and quick retention through natural layers. The utilization of polymers in lipid based definitions for ineffectively dissolvable drugs has been talked about and giving wide scope of uses to enhance the solvency and also disintegration rate of the drug.
REFERENCES:
1. Waterbeemd H, Lennernas H, Artursson P. Drug bioavailability: estimation of solubility, permeability, absorption and bioavailability, Wiley-VCH, Weinheim, Germany, 2003.
2. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutics Drug Classification: The correlation of in-vitro drug product dissolution and in vivo bioavailability. Pharmaceutical Research, 1995; 12:413-420.
3. United States Food and Drug Administration. Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. August 2000. http://www.fda.gov/cder/guidance/361andfnl.htm.
4. Mohd Y, Mohd A, Kumar A, Aggarwal A. Biopharmaceutical Classification System: An Account. International Journal of Pharm Tech Research. 2010; 2(3):1681-1690.
5. Reddy BB, Karunakar A. Biopharmaceutics Classification System: A Regulatory Approach. Dissolution Technologies. 2011; 31-37.
6. Wagh MP, Patel JS. Biopharmaceutical Classification System: Scientific Basis for Biowaiver Extensions. International Journal of Pharmacy and Pharmaceutical Sciences. 2010; 2(1):12-19.
7. Aulton ME, Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, Churchill livingstone, Elsevier, 3rd edition, 2013.
8. Guidance for Industry, Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), August 2000, BP
9. Rohilla S, Rohilla A, Marwaha RK, Nanda A. Biopharmaceutical Classification System: A Strategic Tool for Classifying Drug Substances. International Research journal of pharmacy. 2011; 2(7):53-59.
10. U.S. Food and Drug Administration, 07/04/2017, Available from: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm128219.htm
11. Thiel-Demby VE, Humphreys JE, St John Williams LA, Ellens HM, Shah N, Ayrton AD, Polli JW. Biopharmaceutics classification system: validation and learnings of an in vitro permeability assay. Mol Pharm. 2009; 6(1):11-8.
12. Sugano K, Okazaki A, Sugimoto S, Tavornvipas S, Omura A, Mano T. Solubility and dissolution profile assessment in drug discovery. Drug Metab. Pharmacokinet. 2007; 22:225–254.
13. Bosselmann S, Williams RO. Route-specific challenges in the delivery of poorly water-soluble drugs. in Formulating Poorly Water Soluble Drugs, R. O. Williams III, A. B. Watts, and D. A. Miller, Eds., pp. 1–2, Springer, New York, NY, USA, 2012.
14. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods. 2000; 44:235-249.
15. Johnsonm KC, Swindell AC. Guidance in the setting of drug particle size specifications to minimize variability in absorption. Pharm. Res. 1996; 13:1795-1798.
16. Curatolo W. Physical chemical properties of oral drug candidates in the discovery and exploratory development settings in: Pharmaceutical Science and Technology Today. 1998; 1(9):387-393.
17. Bergström CA, Strafford M, Lazorova L, Avdeef A, Luthman K, Artursson P. Absorption classification of oral drugs based on molecular surface properties. J Med Chem. 2003; 46(4):558-70.
18. Benet LZ, Amidon GL, Barends DM, Lennernas H, Polli JE, Shah VP, Stavchansky SA, Yu LX. The use of BDDCS in classifying the permeability of marketed drugs. Pharm. Res. 2008; 25:483-488.
19. Dressman J, Butler J, Hempenstall J, Reppas C. The BCS: where do we go from here?, Pharm. Technol. 2001; 68-76.
20. U.S FDA, Guidance for Industry, Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system, Washington, DC US Dep. Heal. Hum. Serv. 2000.
21. Oh DM, Curl RL, Amidon GL. Estimating the fraction dose absorbed from suspensions of poorly soluble compounds in humans: A mathematical model. Pharm. Res. 1993; 10:264-270.
22. Takano R, Furumoto K, Shiraki K, Takata N, Hayashi Y, Aso Y, Yamashita S. Rate-limiting steps of oral absorption for poorly water-soluble drugs in dogs; prediction from a miniscale dissolution test and a physiologically-based computer simulation. Pharm. Res. 2008; 25:2334-2344.
23. Butler JM, Dressman JB. The developability classification system: Application of biopharmaceutics concepts to formulation development. J. Pharm. Sci. 2010; 99:4940-4954.
24. Janssens S, Mooter GV. Review: physical chemistry of SDs. J. Pharm. Pharmacol. 2009; 61:1571-1586.
25. Huang Y, Dai WG. Fundamental aspects of SD technology for poorly soluble drugs. Acta Pharm. Sin. B. 2014; 4:18-25.
26. Leuner C, Dressman J. Improving drug solubility for oral delivery using SDs. Eur. J. Pharm. Biopharm. 2000; 50:47-60.
27. Dixit AK, Singh RP. SD: A strategy for improving the solubility of poorly soluble drugs. IJRPBS. 2012; 3(2):960-966.
28. Huda NH, Saffoon N, Sutradhar KB, Uddin R. Enhancement of Oral Bioavailability and SD: A Review. Journal of Applied Pharm Science. 2011; 1:13-20.
29. Jain CP, Sharma A. SD: A promising technique to enhance solubility of poorly water soluble drug. Int. J of Drug Delivery. 2011; 3:149-170.
30. Bowmik D, Harish G, Duraivel S, Kumar BP, Raghuvanshi V, Sampath KP. SD- an approach to enhance the dissolution rate of poorly water soluble drugs. The Pharma Innovation Journal, 2012; 1(12): 24-38.
31. Kumar P. SD – A review. Journal of pharmaceutical and scientific innovation. 2012; 1(3):27-340.
32. Thompson DO. Cyclodextrins Enabling Excipients: their Present and Future Use in Pharmaceuticals. Crit, Rev Ther. Drug Carrier Syst. 1997; 14(1):1-104.
33. Myrdal PB, Yalkowsky SH. Complexation and Cyclodextrin. In: Swarbrick J, editor. Encyclopedia of Pharmaceutical Technology, Informa Health Care, 3rd edition, New York, USA, 2007.
34. Loftsson T, Duchene D. Cyclodextrins and their pharmaceutical applications. International Journal of Pharmaceutics. 2007; 329(1-2):1-11.
35. Chaudhary VB, Patel JK. Cyclodextrin inclusion complex to enhance solubility of poorly water soluble drugs: a review. Int J Pharm Sci Res. 2013; 4(1):68-76.
36. Bader H, Ringsdorf H, Schmidt B. Watersoluble polymers in medicine. Angew Makromol Chem. 1984; 123:457-485.
37. Jones M, Leroux J. Polymeric micellesea new generation of colloidal drug carriers. Eur J Pharm Biopharm. 1999; 48:101-111.
38. Lukyanov AN, Torchilin VP. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Adv Drug Deliv Rev. 2004; 56:1273-1289.
39. Torchilin V. Targeted polymeric micelles for delivery of poorly soluble drugs. Cell Mol Life Sci. 2004; 61:2549-2559.
40. Gaucher G, Dufresne M, Sant VP. Block co-polymer micelles: preparation, characterization and application in drug delivery. J Control Release. 2005; 109:169-188.
41. Kwon GS, Kano TO. Polymeric micelles as new drug carriers. Adv Drug Deliv Rev. 1996 21:107-116.
42. Yokoyama M, Kwon GS, Kataoka K. Preparation of micelle-forming polymer drug conjugates. Bioconjugate Chem. 1992; 3:295-301.
43. Hoes CJT, Potman W, Feijen J. Optimization of macromolecular prodrugs of the antitumor antibiotic Adriamycin. J Control Release. 1985; 2:205-13.
44. Duncan R, Rejmanova PK, Kopecek J. Anticancer agents coupled to N-(2-hydroxypropyl)methacrylamide copolymers I. Evaluation of daunomycin and puromycin conjugates in-vitro. Br J Cancer. 1987; 55:165-174.
45. Endo N, Umemoto N, Hara T. A novel covalent modification of antibodies at their amino groups with retention of antigen-binding activity. J Immunol Methods. 1987; 104:253-258.
46. Muller RH, Peters K, Becker R, Kruss B. Nanosuspension for IV administration of poorly soluble drugs-stability during sterilization and long term storage. Control Release Bioact. 1995; 22:574-575.
47. Leuenberger H. Spray freeze-drying: the process of choice for low water soluble drugs. Journal of Nanoparticle Research. 2002; 4(1-2):111-119.
48. Mumenthaler M, Leuenberger H. Atmospheric sprayfreeze drying: a suitable alternative in freeze-drying technology. International Journal of Pharmaceutics.1991; 72(2):97-110.
49. Williams RQ. Process for production of nanoparticles and microparticles by spray freezing into liquid. US Patent no.20030041602, 2003.
50. Briggs AR, Maxvell TJ. Process for preparing powder blends. US Patent no. 3721725, 1973.
51. Rogers TL, Hu J, Yu Z, Johnston KP, Williams RO. A novel particle engineering technology: spray-freezing into liquid. International Journal of Pharmaceutics. 2002; 242(1-2):93-100.
52. Buxton IR, Peach JM. Process and apparatus for freezing a liquid medium. US Patent no. 4470202, 1984.
53. Purvis MT. Mattucci E, Crisp MT, Johnston KP, Williams RO. Rapidly dissolving repaglinide powders producers by the ultra-rapid freezing process. AAPS PharmSciTech. 2007; 8(3):58.
54. Rasool AA, Hussain AA, Dittert LW. Solubility enhancement of some water-insoluble drugs in the presence of nicotinamide and related compounds. Journal of Pharmaceutical Sciences. 1991; 80(4):387-393.
55. Badwan AA, El-Khordagui LK, Saleh AM, Khalil SA. The solubility of benzodiazepines in sodium salicylate solution and a proposed mechanism for hydrotropic solubilization. International Journal of Pharmaceutics. 1983; 13(1):67-74.
56. Roy BK, Moulik SP. Functions of hydrotropes (sodium salicylate, proline, pyrogallol, resorcinol and urea) in solution with special reference to amphiphile behaviors. Colloids and Surfaces A. 2002; 203(1-3):155-166.
57. Patil SV, Sahoo SK. Pharmaceutical overview of spherical crystallization. Der Pharmacia Letter. 2010; 2(1):421-426.
58. Blagden N, Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Advanced Drug Delivery Reviews. 2007; 59(7):617-630.
59. Aguiar AJ, Krc J, Kinkel AW, Samyn JC. Effect of polymorphism on the absorption of chloramphenicol from chloramphenicol palmitate. Journal of Pharmaceutical Sciences. 1967; 56(7):847-853.
60. Suleiman MS, Najib NM. Isolation and physicochemical characterization of solid forms of glibenclamide. International Journal of Pharmaceutics. 1989; 50(2):103-109.
61. Shefter E, Higuchi T. Dissolution behavior of crystalline solvated and nonsolvated forms of some pharmaceuticals. Journal of Pharmaceutical Sciences. 1963; 52:781-791.
62. Allen PV, Rahn PD, Sarapu AC, Vanderwielen AJ. Physical characterization of erythromycin: anhydrate, monohydrate, and dihydrate crystalline solids. Journal of Pharmaceutical Sciences. 1978; 67(8):1087-1093.
63. Vishweshwar P, McMahon JA, Bis JA, Zaworotko MJ. Pharmaceutical co-crystals. Journal of Pharmaceutical Sciences. 2006; 95(3):499-516.
64. Shan N, Zaworotko MJ. The role of cocrystals in pharmaceutical science. Drug Discovery Today. 2008; 13(9-10):440-446.
65. Hickey MB, Peterson ML, Scoppettuolo LA. Performance comparison of a co-crystal of carbamazepine with marketed product. European Journal of Pharmaceutics and Biopharmaceutics. 2007; 67(1):112-119.
66. Moribe K, Tozuka Y, Yamamoto K. Supercritical carbon dioxide processing of active pharmaceutical ingredients for polymorphic control and for complex formation. Advanced Drug Delivery Reviews. 2008; 60(3):328-338.
67. Pasquali I, Bettini R, Giordano F. Supercritical fluid technologies: an innovative approach for manipulating the solid-state of pharmaceuticals. Advanced Drug Delivery Reviews. 2008; 399-410.
68. Paradkar A, Maheshwari M, Kamble R, Grimsey I, York P. Design and evaluation of celecoxib porous particles using melt sonocrystallization. Pharmaceutical Research. 23(6):1395-1400.
69. Strickley RG. Solubilizing excipients in oral and injectable formulations. Pharm. Research. 2004; 21:201-230.
70. Nema S, Washkuhn RJ, Brendel RJ. Excipients and their use in injectable products. Pharm. Sci. Technology. 1997; 51(166-171).
71. Rubino JT, Yalkowsky SH. Co-solvency and deviations from log linear Solubilization, Pharm. Research. 1987; 4:231-236.
72. Zhao L, Li P, Yalkowsky SH. Solubilization of fluasterone. Journal of Pharmaceutical Science. 1999; 88:967-969.
73. Seedher N, Bhatia S. Solubility enhancement of Cox-2 inhibitors using various solvent systems. AAPS Pharm. Sci. Tech. 2003; 4:33.
74. Koester LS, Bertuol JB, Groch KR, Xavier CR, Moellerke R, Mayorga P, Dalla Costa T, Bassani VL. Bioavailability of carbamazepine: beta cyclodextrin complex in beagle dogs from hydroxy propyl methyl cellulose matrix tablets. Eur.J.Pharm.Sci. 2004; 22(2-3):201-207.
75. Wen X, Tan F, Jing Z, Iiu Z. Prepration and study of the 1:2 Inclusion Complex of Carvedilol with R – Cyclodextrin. Simeoni, Journal of Pharmaceutical and Biomedical Analysis. 2004; 34:517-523.
76. Loftsson T, Masson M. Cyclodextrins in topical drug formulations: theory and practice. International Journal of Pharmaceutics. 2001; 225:15-30.
77. Sato K, Sugibayashi K, Morimoto Y. Species differences in percutaneous absorption of nicorandil. Journal of Pharmaceutical Sciences. 1991; 80:104-107.
78. Sertsou G, Butler J, Scott A, Hempenstall J, Rades T. Factors affecting incorporation of drug into solid solution with HPMCP during solvent change coprecipitation. Int J Pharm. 2002; 245:99-108.
79. Gabmann P, List M, Schweitzer A, Sucker H. Hydrosols-Alternatives for the parenteral application of poorly water soluble drugs. Eur. J. Pharm. Biopharm. 1994; 40:64-72.
80. Nielsen FS, Petersen KB, M¨ullertz A. Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state. European Journal of Pharmaceutics and Biopharmaceutics. 2008; 69(2):553-562.
81. Gursoy RN, Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomedicine and Pharmacotherapy. 2004; 58(3):173-182.
82. Schwendener RA, Schott H. Lipophilic 1-𝛽-D-arabinofuranosyl cytosine derivatives in liposomal formulations for oral and parenteral antileukemic therapy in the murine L1210 leukemia model. Journal of Cancer Research and Clinical Oncology. 1996; 122(12):723-726.
83. Okore VC, Attama AA, Ofokansi KC, Esimone CO. Formulation and Evaluation of Niosomes. Indian J Pharm Sci. 2011; 73(3) .
84. Pouton CW. Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ’self-microemulsifying’ drug delivery systems. European Journal of Pharmaceutical Sciences. 2000; 11(2):S93–S98.
85. Gursoy N, Garrigue JS, Razafindratsita A, Lambert G, Benita S. Excipient effects on in-vitro cytotoxicity of a novel paclitaxel self-emulsifying drug delivery system. Journal of Pharmaceutical Sciences. 2003; 92(12):2411-2418.
86. Mahmoud EA, Bendas ER, Mohamed MI. Preparation and evaluation of self-nanoemulsifying tablets of carvedilol. AAPS PharmSciTech, 2009; 10(1):183-192.
87. Gupta S, Chavhan S, Sawant KK. Self-nanoemulsifying drug delivery system for adefovir dipivoxil: design, characterization, in-vitro and ex vivo evaluation. Colloids and Surfaces A. 2011; 392(1):145-155.
88. O’Driscoll CM. Lipid-based formulations for intestinal lymphatic delivery. European Journal of Pharmaceutical Sciences. 2002; 15(5):405-415.
89. Hauss DJ. Oral lipid based Formulations-Enhancing the Bioavailablity of Poorly water soluble drugs. In Drugs and Pharmaceutical Sciences. vol. 170, Informa healthcare,NC, USA, 2007.
90. Charman WN, Porter CJ, Mithani S, Dressman JB. Physiochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH. J Pharm Sci, 1997; 86:269-282.
91. Lobenberg R, Amidon GL. Modern bioavailability, bioequivalence and Biopharmaceutics classification system. New Scientific approaches to international regulatory standards. Eur J Pharm. Biopharm. 2000; 50:3-12.
92. Winstanley PA, Orme MLE. The effects of food on drug bioavailability. Br J Clin Pharmacol. 1989; 28:621-628.
93. Leblanc MJ, Brunet S, Bouchard G. Effects of dietary soybean lecithin on plasma lipid transport and hepatic cholesterol metabolism in rats. Journal of Nutritional Biochemistry. 2003; 14(1):40-48.
94. Nicolosi RJ, Wilson TA, Lawton C, Handelman GJ. Dietary effects on cardiovascular disease risk factors: beyond saturated fatty acids and cholesterol. Journal of the American College of Nutrition. 2001; 20(5):421-427.
95. Hany A, E. Shemy. Soybean and health, In Tech Janeza Trdine 9, 51000 Rijeka, Croatia, 2011.
96. Miranda DT, Batista VG, Grando FC, Paula FM, Felicio CA, Rubbo GF, Fernandes LC, Curi R, Nishiyama A. Soy lecithin supplementation alters macrophage phagocytosis and lymphocyte response to concanavalin A: a study in alloxan-induced diabetic rats. Cell Biochemistry Function. 2008; 26(8):859-65.
Received on 20.08.2019 Modified on 16.10.2019
Accepted on 11.11.2019 © RJPT All right reserved
Research J. Pharm. and Tech. 2020; 13(8):3918-3928.
DOI: 10.5958/0974-360X.2020.00694.0