INTRODUCTION:

Today's novel pharmaceutical chemicals are weakly water soluble, resulting in poor bioavailability and ineffective therapy when they are used. Many drugs are available as solid organic molecules, which complicates their administration. The development and improvement of solubility, dissolving rate, and bioavailability has received more attention. In some cases, the experimental settings and nucleation rate of various modifications, i.e. the material's thermal prehistory, have a major impact on the development of solid-state modifications¹.

The development and preservation of metastable solid-state modifications is fraught with difficulties. Polymorphs with various stabilities may spontaneously transition from a metastable to a stable state when exposed to a heat gradient^2-3. The formation of various polymorphic forms is mostly due to changes in crystallisation conditions. This includes the effect of the solvent, the presence of impurities that favour the development of metastable polymorphs, the level of super saturation, temperature, covalent bond geometry, and changes in stirring conditions^4-6. Greater solubility and bioavailability of polymorphous modifications are linked to the creation of crystals that affect the properties of original substances. Changes in the polymorph structure affect the physicochemical and pharmacological properties of their melting points, solubility, dissolution rate, lattice structure, hardness, stability, and a few other parameters differ. Simultaneous research employing multiple experimental methodologies found to be required to understand the process of solid alteration formation as well as determine the crystal structure8. Greater solubility and bioavailability of polymorphous modifications are linked to the creation of crystals that affect the properties of original substances. Changes in the polymorph structure affect the physicochemical and pharmacological properties of their melting points, solubility, dissolution rate, lattice structure, hardness, and stability⁷. Simultaneous research employing multiple experimental methodologies found to be required to understand the process of solid alteration formation as well as determine the crystal structure⁸. The current review focuses on a key notion of crystallisation, as well as the principles of crystal obstacle, which are often used to alter crystal shape and size, and polymorphic form in the formulation. Although the crystalline state and its characterisation with their modification, could aid in their dissolving behaviour and bioavailability are considered to be an important parameter.

CATEGORY OF POLYMORPHISM:

The polymorphism is classified as Enantiotropic or Monotropic depending on its stability, which is controlled by a wide range of pressure and temperature⁹. (Figure 1)

Figure 1: Graph of free energy vs temperature of Monotropic and Enantiotropic.

Enantiotropic polymorphs are kinetically reversible, meaning they may be transformed from one form to another that is stable under a variety of temperature and pressure circumstances. This may be seen in the free energy temperature graph, where one polymorph is changed into another by crossing point¹⁰. Through a physical and thermal procedure, these can be swapped out. The rate of cooling determines the formation of metastable polymorphs, which are thermodynamically unstable¹¹. This is due to a point where the free energy of two forms is equal to their transition temperature. In such circumstances, one form has a lower enthalpy due to their lattice arrangement in exothermic polymorphs, while the other form has a stable shape due to the lack of internal energy. The alternative type has a higher enthalpy because of its distinct lattice and unit cell configurations, which are endothermic in terms of temperature and pressure range¹². Monotropic polymorphs are kinetically irreversible because one polymorph is stable throughout all temperature and pressure ranges, whereas the others are unstable. The graph of free energy – temperature, where the curves do not cross, explains this phenomenon¹³. This is because of their molecular structure and energy of two forms is equal to their transition temperature. In such circumstances, one form has a lower enthalpy due to their lattice arrangement in exothermic polymorphs, while the other form has a stable shape due to the lack of internal energy. The alternative type has a higher enthalpy because of its distinct lattice and unit cell configurations, which are endothermic in terms of temperature and pressure range. Monotropic polymorphs are kinetically irreversible because one polymorph is stable throughout all temperature and pressure ranges, whereas the others are unstable. This phenomenon is explained by the graph of free energy – temperature, where the curves do not cross each other. This is because of their molecular structure. One form shows its free energy less than the other polymorphs in the range below its melting point. Most of the polymorph which exhibits exothermic is monotropic as there will not possess internal energy because the energy in the crystal lattice is liberated which are thermodynamically stable¹⁴. Conversely, they have no noticeable change in temperature, yet there is a hypothetical progress point that can be determined utilizing the Bauer-Brandl equation.

Where ΔH^T_{m, I}and ΔH^T_m,
II are melting enthalpy of form I, and II, respectively, and T_{m, I}and T_{m, II} are melting points of form I and II respectively.

CHALLENGES FACED IN FORMULATING POLYMORPHIC DRUGS:

More than half of all active pharmaceutical ingredients (APIs) are projected to have several polymorphic forms. As a result, most medications are poorly soluble, which is one of the main biopharmaceutical concerns that affects the drug's bioavailability, therapeutic, and safety¹⁵. The API was not present in a soluble or insoluble state in either the solid or liquid dosing form of the pharmaceutical product. On account of their concentration, solvent, seeding of nucleation, presence of impurities, and their domain temperature and pressure there might be changes in the unit crystal lattice¹⁶. The arrangement of the unit cell in the crystal was changed which convert from one form to another polymorphic form¹⁷. This converted form was contemplated as the most stable form at the above-considered circumstance. Different physical properties of various polymorphism is depicted in figure 2.

Figure 2: Different physical properties of various polymorphism

Solid dosage form:

The discovery and characterization of a drug substance's diverse solid forms provide alternatives for selecting a form with the right combination of important qualities for expansion into a formulation. Importantly, the intended characteristics may differ depending on the mode of delivery (i.e., oral, pulmonary, parenteral, transdermal, etc.), hence the solid form for each optimum dosage form may be different. Given these alternatives, pharmaceutical solid forms selection and design can be vital to effective drug development¹⁸. It was the front runner in developing a drug product due to its physical, mechanically stronger, and most stable than another dosage form. Some of the Pharmaceutical solid dosage forms are powders, granules, tablets, capsules, lozenges, suppositories, sachets, pills, and pastilles¹⁹. Still, it was contemplated as the most stable dosage form they had a distinctive issue on manufacturing and formulating the solid dosage form. A large percentage of the medicine found in the pharmaceutical is crystalline and that exhibit different polymorphism^20-21. There may be differences in the unit crystal lattice arrangement they establish a kinetically unstable with the effect of temperature, humidity, and excipient on the chemical process and phase transition. Process-induced phase transition can be predicted using preformulation studies when developing manufacturing procedures for solid dosage forms²². By choosing the right process, these alterations can be managed and avoided. For example, Novobiocin was employed as the crystal form in tablet and capsule formulations that is active but shows instability in a solution, however, crystalline acidic Novobiocin was poor absorption and does not achieve sufficient systemic levels when taken orally. Induced hardening in tablets is expected to reduce dissolution rates in formulations having a high quantity of crystalline excipients like mannitol after storage. Understanding the mechanism of phase transitions aids in understanding the potential for such shifts as well as the elements that influence their kinetics²³. This level of mechanistic understanding allows for more logical formulation design and the selection of robust methods to assure consistent product manufacturing and performance.

Liquid dosage form:

There are liquid dosage formulations that are monophasic or biphasic. In a monophasic liquid dosage form, there is only one phase: a full solution. A true solution is a liquid containing a uniform mixture of solids, liquids, and gases²⁴. In a biphasic liquid dose form, there are two stages. Aromatic water, collodion, draught, ear drop, nasal drop, elixirs, mixes, emulsions, suspension, enemas, gargles, injections, irrigations, linctuses, liniments, lotions, mouthwashes, sprits, sprays, syrups, tinctures, and paintings were among the pharmaceutical liquid dosage types²⁵. When using the improper polymorph of a drug, it can cause a polymorphic transition from one form to a stable polymorph. As a result, (a) Crystal growth occurs, resulting in an undesirable particle size distribution. (b) Caking, this causes suspensions to be difficult to re-suspended evenly²⁶. One of the first things to consider when preparing a solution is the solubility of the medicine in the vehicle. The solid phase present determines the intrinsic solubility of a chemical (solvate or anhydrate). Since cross section energies of actual structures (shapeless, polymorphs of solvates) are responsible for the difference in solubilities and disintegration percentage, the most notable distinction in solvency is noticed between undefined and glasslike materials^27-28. When a metastable form of the medicine is utilised to determine solubility and the medication concentration in the framework exceeds the balance solvency of a less dissolvable kind of the medication, a thermodynamically unstable formulation develops. In the drug product of a parenteral solution, the water solubility of a compound was determined, and the component was found to be suitably soluble for the concentration required in the formulation. During stability testing on the formulation, the presence of a precipitate was quickly found. According to the research, the precipitate was a chemical polymorph that was less soluble²⁹.

Semi-solid dosage form:

Pharmaceutical semisolid formulations are topical drugs applied to the skin or exposed mucous membranes to produce localised and, in certain cases, systemic effects³⁰. Semisolid dosage forms, in general, are complicated formulations with complex structural features. Semisolid pharmaceutical dose forms include creams, jellies, ointment, paste, suppositories, and ophthalmic ointment. Because polymorphs differ in chemical stability, solubility, crystal shape, melting point, and a number of other characteristics, it's vital to figure out if polymorphs exist for the innovative drug under study^31-32. When creams are manufactured with the active ingredient suspended in the cream base, the changed polymorph can cause a stage reversal. The vehicle then evolved precious polymorphic formation, resulting in gritty, cosmetically unattractive creams. The correct system is to choose the polymorphic stage that dissolves the least in the cream base. When a metastable stage with high dissolvability is suspended in cream base, there is a significant risk of nucleation of a more stable (less solvent) structure³³. The crystal size decreases as the stable form takes over from the metastable stage. A change in the melting properties of a suppository base may result from polymorphism changes. If the suppository foundation relies on melting at body temperatures to release the API from the formulation, even a slight shift in melting point could cause major issues. A low melting point product may melt or soften at shelf temperatures³⁴. When the suppository is given, it may not dissolve properly. The reported polymorphs and pseudo-polymorphs of recent research out comes are tabulated in table 1.

Table 1. Reported polymorphs and pseudo polymorphs observed with drug

Drug	Modifications	Solid phase	Recrystallization solvent	Method	Outcome
Nicotinamide	Form 1-triclinic Form 2-orthorhombic	co-crystal	Nioctinamide : Pimelic acid (1:1), Methanol	slow solvent evaporation	The polymorphic transition of form 1à2³⁵.
Ciprofloxacin	Form I	monohydrate	Salicylic acid, Water: Ethanol (1:1 v:v)	Fritsch planetary micro mill	The grinding process' creation pathway and kinetics are determined to be dependent on the initial material's form and reaction circumstances. The dehydration of hydrated salts revealed a two-step mechanism that involves the creation of a separate intermediate crystalline product³⁶.
	Form II	monohydrate	Salicylic acid, Water: organic solvent (1:1 v/v) Methanol, Ethanol, Isopropanol, Acetonitrile.
	-	solvate	Salicylic acid, Methanol
	-	solvate	Salicylic acid, Acetonitrile
	CIP	hydrate salts	Water	slurry method
Celecoxib	Form I	-	Storing melt quench amorphous sample in 40°C	melt quenching	Cross-nucleation has also been seen between CEL polymorphs form I and III, which have distinct crystal growth rates in the diffusion-controlled region on the surface and in the bulk³⁷.
Celecoxib	Form III	-	Storing melt quench amorphous sample in 80°C	melt quenching
Phenazopyridine	Form I	salt	Dihydrobenzoic acid, Ethanol was slurred with Acetonitrile	slurring method	The two polymorphs are enantiotropically related. They exhibit different but significantly improved aqueous solubility³⁸.
Phenazopyridine	Form II	salt	i) Form I in water ii)Dihydrobenzoic acid was slurred with acetonitrile	slurring method
Ethionamide	ETH⁺SAL^-	salt	Salicylic acid, few drops of Methanol, Isopropanol: Methanol (1:3)	seeding crystallization	The two polymorphs were found to be enantiotropically related. In terms of dissolving rate, the two forms are close to one other, however the pure ETH performs substantially better³⁹.
Ethionamide	ETHSAL	co-crystal	Methanol	rapid evaporation
Islatravir	Form I	anhydrate	Ethylene vinyl acetate, Polycaprolactone	hot-melt extrusion	The rate of water loss as well as water entrapment in a heating vessel is prominent factors in phase conversion into distinct anhydrate polymorphs for a crystalline hydrate phase. It was concluded that in the early stages of pharmaceutical research, discovery of thermodynamically stable anhydrate forms is important⁴⁰.
	Form II	anhydrate	Heated from 20-150°C using DSC	thermal conversion
	Form IV	anhydrate	Methyl cyanide, Water, Acetonitrile	hot solution crystallization
Clevudine	Form I	solvate	Ethyl acetate	solvent evaporation	The water solubility of the three clevudine polymorphs is not considerably different. It was discovered that both Forms 1 and 3 underwent eventual change to Form 2 during dissolution studies at 25°C, and that Form 2 was established as the stable form at temperatures below 175°C⁴¹.
	Form 2	-	Cinnamamide, Ethyl acetate, Acetonitrile	liquid-assisted grinding
	Form 3	-	Heating the sample at 192°C	Hot-melt extrusion

Sulfamethazine	SMT-SAC Form I	Co-crystal	Saccharine, Acetonitrile	slow evaporation method	Moisture sorption and compaction parameters of the cocrystal Form II were noticeably different, which could influence the solid form chosen for further tablet development⁴².
Sulfamethazine	SMT-SAC Form II	Co-crystal	Saccharine, Acetonitrile: water (99:1 v/v)	slow evaporation method
Levofloxacin	Form α	solvate	Dimethylsulfoxide (DMSO)	solvent evaporation	Variable-temperature powder X-ray diffraction was used to explore the phase change between distinct solid-state crystal forms of levofloxacin. The newly discovered solvates can be directly dehydrated to anhydrous form, which can then be converted back to anhydrous form by heating ⁴³.
	Form α	solvate	Dimethylsulfoxide (DMSO)	cooling crystallization
	Acetic acid	solvate	Glacial acetic acid	solvent evaporation
	-	solvate	n-propanol	slow cooling crystallization
	-	solvate	n-propanol, acetonitrile	slow cooling crystallization
	-	solvate	Ethylene glycol	slow crystallization
	-	solvate	Ethylene glycol, Acetonitrile	slow cooling crystallization
	LM	Monohydrate	Acetonitrile and water	slow cooling crystallization
Praziquantel	PZQ-A	solvate	Acetone	solvent evaporation	The creation of a novel phase, the pseudo-polymorphic form PZQ-MH, is confirmed by microscopic, spectroscopic, thermal, diffractometric, and functional investigations. His work could influence the development of new and enhanced API functional derivatives⁴⁴.
	PZQ-AM	solvate	Placed in a vacuum oven a 150°C	slow solvent evaporation
	PZQ-MH	solvate	Placed in a vacuum oven a 150°C and 60mm Hg, then kept in a freezer (-20°C)	cooling crystallization
Efavirenz	Form I	Solvate	Acetonitrile	solvent evaporation method	The thermodynamic monotropy of EFV forms I and II has been demonstrated. The Arrhenius plot revealed that the activation energy of the transition under isothermal treatment was 23.051 kJ mol-1, and that the half-life of form II at ambient temperature was 428.05 min ( approx. 7.1h) ⁴⁵.
Efavirenz	Form II	Solvate	n-hexane	solvent evaporation method
Rifampicin	RFEtOHCryst1	solvate	Ethanol	spray drying process	The formation's aerosol performance and storage stability were tested, and all samples demonstrated stable aerosol performance. Over a six-month period, the chemical stability of samples spray dried from ethanol was found to be satisfactory, while samples spray dried from methanol or water showed considerable degradation ⁴⁶.
	RFEtOHCryst2	solvate	Ethanol
	RFMeOHCryst1	solvate	Methanol
	RFaqCryst1	hydrate	Water
Pyrazinamide	Form α	solvate	Acetonitrile	solvent evaporation	Fixed dose combinations fortified with form and form yielded 0.78, 0.88, and 0.98 w/w of form, respectively. It demonstrates a viable approach for ensuring PZA polymorphism purity throughout the entire pharmaceutical manufacturing process ^47,48.
	Form β	solvate	Dioxane, dichloromethane	slow solvent evaporation
	Form δ	solvate	Acetone	solvent evaporation
	Form γ	solvate	sample was kept at 170°C	Hot extrusion method
Sitagliptin	STGA	Anhydrous	Placed in vacuum at 150C with 300-400mmHg	Hot extrusion method	There was a minor difference in thermal stability between sitagliptin phosphate monohydrate and sitagliptin phosphate anhydrous; nonetheless, both are more thermostable than the basic molecule ⁴⁹.
Sitagliptin	STGB	Anhydrous	Water, ammonia, ethyl acetate	slow solvent evaporation
Niflumic acid	NIF-CAF Form I	Co-crystal	Caffeine, dichloromethane	ball milling technique and evaporation	When compared to NIF-CAF form II, the polymorph NIF-CAF form I has better solubility and a faster dissolution rate. NIF-CAF form II is also much more stable than form I ⁵⁰.
Niflumic acid	NIF-CAF Form II	Co-crystal	Caffeine, acetonitrile	ball milling technique and evaporation
Bisoprolol	Form I	Polymrophs	Acetone, fumaric acid	cooling crystallization	At 40-45 °C, thermodynamic stability investigations revealed an enantiotropic connection between form I and II polymorphs. All of the produced forms are extremely soluble, according to solubility tests ⁵¹.
	Form II	polymorphs	Acetone	cooling crystallization
	-	Hydrate	Potassium nitrate, water and kept at 30-60% RH	-
Ganciclovir	GCV	Solvate	Dimethyl formamide, methanol, water	solvent evaporation technique	GCV exists as two inversion-related conformers in form I and a single chiral conformer in form II in the crystalline state. The hydrogen bonds in form I are exclusively intermolecular, but in form II they are both inter- and intramolecular, explaining the differences in molecular conformations between the two polymorphs ⁵².
Ritonavir	Form I	Solvate	Acetone, isopropanol, toluene	rapid cooling technique	With more effective intermolecular packing, decreased void space, and greater density, Form I is more stable and polarised. Although Form II is less stable, because its conformation is both donor and acceptor, it has a strong hydrogen bonding connection and a more stable crystal structure ⁵³.
Ritonavir	Form II	Solvate	Acetone, isopropanol, toluene	cooling crystallization
Isavuconazole	ISV	Solvate	Methanol	cooling crystallization	It was discovered that when crystalline isavuconazole is dissolved, it does not turn into hydrate. In pharmaceutically relevant buffer environments, the amorphous and salt forms of ISV showed a spring-like rise in drug concentration. The pharmaceutical salts are tableted, resulting in a delayed phase change into the ISV hydrate and longer drug super saturation ⁵⁴.
	ISV-H₂O	Monohydrate	2-propanol and water (3:1, v:v)	slow cooling crystallization
	ISV-P	-	Phosphoric acid, ethanol	slurry method
	ISV-TS-ACN	Solvate	p-toluenesulfonic acid, acetonitrile	slow cooling crystallization
Rivaroxaban	Form II	-	Tetrahydrofuran, n-heptane	solvent evaporation technique	The Prout-Tompkins and Avrami-Erofee equations, which are solid state kinetic models, provided a reasonable correlation of the phase transformation process from form I to form II. Temperature, slurry density, and stirring speed all improved the rate of transformation ⁵⁵.
Ivabradine hydrochloride	ICISM	Cocrystal	(S)-mandelic acid, ethanol, ethyl acetate.	slurry method	During the wet granulation process, in situ creation of the co-crystal was obtained. When compared to pre-made co-crystal formation, the following formulation experiments revealed that in situ created co-crystal had no effect on the overall stability of the bulk ⁵⁶.
Ivabradine hydrochloride	ICIRM	Cocrystal	(R)-mandelic acid, ethanol, ethyl acetate.	slurry method
Hydroxyprogesterone caproate	Form A	solvate	Methanol, ethanol, isopropyl alcohol, acetone, t-butyl ether, ethyl acetate, acetonitrile, cyclohexane, dichloroethane, toluene, tetrahydrofuran, acetic acid.	i) Evaporative crystallization, ii) anti-solvent crystallization, iii) cooling crystallization.	Form A's crystalline structure revealed a third conformational polymorph that exists exclusively at -133 to 143°C; this monoclinic form was dubbed Form C, and when warmed to ambient temperature, it transforms back to Form A. These researches have improved our knowledge of this medicine and how polymorphs may alter its physical stability in various dose forms ⁵⁷.
Hydroxyprogesterone caproate	Form B	solvate		i) solution-mediated transformation ii)crystallization from melt iii) epitaxial growth crystallization
Sulfasalazine	Form I	solvate	Acetone, acetic acid, acetonitrile, anisole, 2-butane, dichloromethane, dimethyl sulfoxide, ethanol, ethyl acetate, ethylene glycol, methanol, 1-methyl-2-pyrrolidinone, N,N-dimethylacetamide, N,N-dimethylformamide, N-heptane, tetrahydrofuran, toluene.	supercritical antisolvent process	The mixture critical point is favourable for supercritical antisolvent recrystallization of sulfasalazine. These findings show that the supercritical antisolvent technique is a useful tool for controlling and changing sulfasalazine's solid-state properties ⁵⁸.
Acyclovir	ACV-MAL form L	Co-crystal	(L) Maleic acid, methanol	slow solvent evaporation	The temperature at which the phase shift occurs is slightly lower than room temperature, but within the range of ambient temperature. This serves as a reminder that due to its fundamental and practical importance, more attention should be made to pharmacological polymorphism at such temperatures ⁵⁹.
Acyclovir	ACV-MAL form R	Co-crystal	(R) Maleic acid, methanol	slow solvent evaporation
Fasoracetam	Form I	hydrate	water	solvent evaporation	The hydrate form I, with a melting point of 57°C, is found to be the most stable. This low melting point, when combined with the possibility of water losses, could present issues while synthesising the hydrate form and have an impact on the compound's storage conditions ⁶⁰.
	Form II	hydrate	methanol	solvent evaporation
	-	anhydrous	kept at 60°C for one week	hot extrusion
Mefenamic acid	-	solvate	Ethyl acetate	solvent evaporation	Strong solute-solute and solute-solvent interactions were seen in the simulated results. These findings demonstrated the presence of a hydrogen link in polymorphic form I of mefenamic acid during crystallisation with ethyl acetate as a solvent, which aids in the solvation and creation of the hydrogen motif ⁶¹.
Azithromycin dehydrate	Amorph I	Amorphous	At first kept at 413°C followed by super cooling at 100 K min ^-1to 25°C	thermal conversion	Solubility tests conducted in distilled water at 310 K revealed a 1.5-fold increase in solubility. Thermally driven amorphization requires energy to destroy intermolecular hydrogen bonds, according to single-crystal XRD. Interaction by bridging water. Molecules in addition to hydrogen bond interactions between neighbouring azithromycin molecules in unit cell ⁶².
	Amorph II	anhydrate	Heating the compound to 378 K followed by isothermal segment set at 0, 6, 16, and 24 h. Followed by super cooling to 298 K	thermal dehydration technique
	-	anhydrate	The compound was heated to 353 K and kept isothermal for 30 min. Now anhydrate was super cooled to 298 K and reheated to 413 K.	thermal dehydration technique
	-	hemihydrate	Heated in DSC to 323 K and held isothermally for 2h then supercooled to 298 K and reheated to 413 K.	thermal dehydration technique
Aceclofenac	-	solvate	Acetone, ethanol, methanol and Propranolol	cooling crystallization	Crystals formed from ethyl acetate and acetone showed enhance solubility and dissolution profile ⁶³.
Norfloxacin	Form I	solvate	Methanol and 1% acetic acid	cooling crystallization	Crystals exhibited increase in solubility and dissolution rate ⁶⁴.
Tinidazole	-	solvate	Methanol	emulsion solvent evaporation	Crystals exhibited increase solubility and dissolution rate ⁶⁵.
Nifedipine	Incorporated in solid lipid nanoparticles	solid lipid nanoparticles	95% ethanol	Nano-precipitation method	Increase in dissolution rate and increase in oral bioavailability by two times ⁶⁶.

CONCLUSION:

For the creation and manufacturing of high-quality and stable medical components and products, polymorphism study and characterization are essential. Because different polymorphs have varying thermodynamic properties, packing characteristics, kinetic qualities, spectroscopic properties, mechanical properties, and surface properties, the correct features are required for the drug's bioavailability. Medication polymorphism and the production of polymorphous crystals to improve drug solubility and bioavailability have piqued the interest of individual scientists as well as pharmaceutical companies. Understanding the physics of polymorphism has progressed dramatically in recent decades, allowing crystal level design of pharmacological API and more control in the desired forms. Polymorph control has evolved from a cryptic method to an effective tool for resolving problems that arise during drug development.

CONFLICT OF INTEREST:

The authors declare there is no conflict of interest.

ACKNOWLEDGMENT:

The authors would like to thank the Department of Science and Technology - Fund for Improvement of Science and Technology Infrastructure (DST-FIST) and Promotion of University Research and Scientific Excellence (DST-PURSE) for the facilities provided for conducting the research.

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Received on 22.06.2022 Revised on 15.02.2024

Accepted on 07.02.2025 Published on 10.02.2026

Available online from February 16, 2026

Research J. Pharmacy and Technology. 2026;19(2):895-904.

DOI: 10.52711/0974-360X.2026.00127

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