Formulation and Evaluation of Solid Self-Nanoemulsifying Drug Delivery System for Enhancing the Solubility and Dissolution Rate of Budesonide

 

Kanuri Lakshmi Prasad, Dr. Kuralla Hari*

Department of Pharmaceutical Technology, Maharajah’s College of Pharmacy, Phool Baugh,

Vizianagaram - 535002 (Andhra Pradesh).

 

ABSTRACT:

Objective: To enhance solubility and dissolution rate of budesonide through development of solid self-nanoemulsifying drug delivery system (S-SNEDDS).

Methods: Liquid self-nanoemulsifying drug delivery systems (L-SNEDDS) were prepared and ternary phase diagram was constructed using Origin pro 8. Liquid self-nanoemulsifying formulation LF2 having 20% oil and 80% of surfactant/co-surfactant was optimized from the three formulations (LF1-LF3) to convert in to solid, through various characterization techniques like self-emulsification, in vitro drug release profile and drug content estimation. The prepared L-SNEDDS converted into S-SNEDDS, SF1-SF6 by adsorption technique using Aerosil 200, Neusilin US2, and Neusilin UFL2 to improve flowability, compressibility and stability.

Results: Formulation LF2 exhibited globule size of 82.4 nm, PDI 0.349 and Zeta potential -28.6 mV with drug indicating the stability and homogeneity of particles. The optimized formulation SF4 containing Neusilin UFL2 was characterized by DSC, FTIR, X-Ray diffraction studies and found no incompatibility and no major shifts were noticed. Formulation SF4 released 100 % drug in 20 min against pure drug release of 47 % in 60 min. Regardless of the form (i.e. liquid or solid) similar performance of emulsification efficiency is observed.

Conclusion: The results demonstrated that the technique of novel solid self-nanoemulsifying drug delivery system can be employed to enhance the solubility and dissolution rate of poorly water-soluble drug budesonide.

 

 

INTRODUCTION:

Inflammatory bowel diseases (IBD) Ulcerative colitis and Crohn’s disease cause the inflammation of mucosa in the small and large intestine. Development of drug delivery to both conditions at a time is preferred. A drug, only in its dissolved form, can be absorbed into stomach and intestine¹. Budesonide is a locally acting corticosteroid with high affinity for glucocorticoid receptors. It offers several therapeutic advantages such as negligible oral bioavailability, rapid clearance and no formation of active metabolites and hence preferred over old steroids such as hydrocortisone, prednisolone and dexamethasone for the localized treatment of IBD. However, budesonide has poor solubility and bioavailability, which limits its dissolution and therapeutic potential².

 

Self-Nanoemulsifying drug delivery systems (SNEDDS) are isotropic mixtures of drug, lipids and surfactants, usually with one or more hydrophilic co-solvents or co-emulsifiers.

 

Upon mild agitation followed by dilution with aqueous media, these systems can form fine emulsion instantaneously. ‘SNEDDS’ is a broad term, typically producing emulsions with a droplet size <100 nm. Self-Emulsifying formulations spread readily in the GI tract, the digestive motility of the stomach and intestine provide the agitation necessary for self-emulsification^3,4. Rapid emulsion formation helps to keep the drug in soluble form whereas the high surface area provided by the small droplets enables more efficient drug transport through the membrane leading to improved oral bioavailability⁵. These formulations have been shown to reduce the slow and incomplete dissolution of a drug, facilitate to solubilized phase formation, increase the transportation extent  via the intestinal lymphatic system and bypass the P-gp efflux and augmenting absorption of drug from the GI tract^2,6,7,8.

 

MATERIALS AND METHODS:

Materials: Budesonide from Avik Pharma, Mumbai, Capryol 90, Labrafil M 1944 CS and Transcutol HP from Gattefosse India, and Neusilin US2, Neusilin UFL2 from Gangwal Chemicals, Mumbai, received as gift samples. Kolliphor RH 40 received from BASF.

 

Solubility studies:

Solubility of Budesonide was determined in various oils (viz. Aniseed oil, Castor oil, Capryol 90, Cinnamon oil, Oleic acid, Peppermint oil, Lemon oil), Surfactants (viz. KolliphorRH40, Labrafil M 1944CS, Tween 80, Span 80), Co-surfactants/Co-solvents (viz. Propylene Glycol, PEG 200, PEG 400, Transcutol HP), water and buffers pH 6.8, 0.1N HCl. An excess amount of the drug was added to each of the selected vehicle, stirred in Cyclomixer followed by Water bath shaker for 72 h at 37 ̊C followed by centrifugation for 15 min at 3000 rpm. 1 ml of supernatant obtained was diluted suitably with ethanol and estimated by UV Spectrophotometer at 245 nm^9,10,11.

 

Construction of Ternary Phase Diagram:

Based on the observations of solubility studies, a series of self-emulsifying systems with varying concentrations of oil (10-40%) and S-Mix (a mixture of both surfactant and Co-surfactant 10-80%) were taken¹². S-mix was prepared in different ratios of (1:1, 2:1, 1:2) of surfactant/Co- surfactant respectively. S-mix ratios were selected and then it was combined with oil in different ratios of Oil-S-mix such as 1:9, 2:8, 3:7, 4:6, 5:5, 6:4, 7:3, 8:2 and 9:1 respectively¹³. Each homogenous oily mixture sample was then diluted with purified water. Samples that could easily spread in water and form a fine emulsion were considered in the microemulsion / nanoemulsions regions and kept for 2 h and the transmittance was determined at 638 nm using UV–visible spectrophotometer. Ternary phase diagram was plotted using the above criteria using Origin pro 8 trial version. Finally, appropriate percentages of oil and S-Mix were selected for preparation of SEDDS formulation^14,15.

 

Drug loading in to Self-Emulsifying formulations:

Once the Self-Emulsifying region was identified, the desired component ratios of Self-Emulsifying formulations were selected for drug incorporation and further optimization. Budesonide (9 mg) was added to oil into a screw-capped glass vial and heated in a water bath at 40 ̊C followed by Surfactant and Co-surfactant and sonicated for 15 min and stored at room temperature for subsequent studies^15,16.

 

Characterization Techniques of formulations:

Self-Emulsification time / Visual assessment:

Self-Emulsification time of SNEDDS was estimated by USP type II dissolution apparatus (Electro lab TDT-08L) by adding drop wise 500 mg of each formulation to 500 ml distilled water at37±0.5 ̊C and at 50 rpm^17,18. Provided gentle agitation and the time required for the formation of emulsion is noted. The resulting mixture was evaluated for precipitation and phase separation for 12, 24, 48 h^19,20,21.

 

Phase separation and drug precipitation study:

The formulations of budesonide loaded SNEDDS were diluted 10, 100 and 1000 times with distilled water, 0.1N HCl and pH 6.8 phosphate buffer. These dilutions were kept for 24 h and observed visually for turbidity, phase separation and drug precipitation²².

 

Centrifugation test:

The liquid SNEDDS preparation diluted 100 times with distilled water then subjected to centrifugation (5000 rpm for 30 min) and observed for any change in homogeneity of Nanoemulsions²².

 

Cloud point measurement:

The formulation diluted 100 folds with distilled water maintained at 25 ̊C with gradual increase of temperature at a rate of 5 ̊C / min and the corresponding cloud point temperatures were read at first sign of turbidity by visual observation^23,24.

 

Percentage transmission measurement:

The formulation (100 mg) was diluted into 100 ml of distilled water, 0.1 N HCl and pH 6.8 phosphate buffer solutions. Percent transmission was measured by UV spectrophotometer at 628 nm in triplicate²⁵.

 

Droplet size and PDI determination:

The droplet size of micro/nanoemulsions is determined by photo correlation spectroscopy using a Horiba Nano Partica SZ-100 which can measure sizes between 0.3 nm – 8 μm. PDI is a measure of particle homogeneity vary between 0.0-1.0. The formulation was diluted 100 folds with distilled water and stirred for 5 minutes^26,27.

 

Zeta potential:

To identify the charge of the particles this technique is used. The formulation was diluted 100 folds with distilled water and zeta potential was determined using zeta meter^28,29.

 

Drug content determination:

SNEDDS formulation equivalent to 9 mg of budesonide was dissolved in pH 6.8 phosphate buffer. Resultant solution was diluted appropriately and drug content was analyzed by UV-spectrophotometer²⁹.

 

Turbidity measurement:

The growth of emulsification is measured by colorimeter at 510 nm. SNEDDS formulation, 0.5 ml introduced into 250 ml of distilled water using magnetic stirrer at constant speed at room temperature³⁰.

 

 

Refractive index:

The SNEDDS formulations diluted 100 folds with distilled water. If refractive index of the system is similar to the refractive index of the water (1.333), then formulation has transparent nature^31,32.

 

In-vitro drug dissolution studies from liquid SNEDDS:

The in vitro dissolution test was performed in 900 ml dissolution medium 0.1 N HCl and 6.8 pH phosphate buffer maintained at 37 ̊C using USP dissolution test apparatus II rotating at 50 rpm (Electrolab TDT 08L). The L-SNEDDS formulations were filled in a capsule for drug release studies. Samples (5 ml) were withdrawn and replaced with fresh media after 5, 10, 15, 20, 30, 45 and 60 min were analyzed spectrophotometrically for budesonide at 245nm. Cumulative drug dissolution at different time intervals was plotted versus time²⁰.

 

Preparation of solid self-nanoemulsifying drug delivery system:

The liquid SNEDDS with acceptable emulsification efficiency and high dissolution parameters selected for preparation of solid SNEDDS by adsorption with carriers Aerosil 200, Neusilin US2, and Neusilin UFL2  to get free flowing powder and evaluated for flow properties^33,34. Six solid formulations were prepared containing SF1 (Aerosil 200,Crospovidone), SF2 (Aerosil 200, Croscarmellose Sodium), SF3 (NeusilinUFL2,Crospovidone), SF4 (NeusilinUFL2,Croscarmellose Sodium), SF5 (NeusilinUS2,Crospovidone), SF6 (NeusilinUS2, Croscarmellose Sodium).

 

Oil adsorption capacity:

It is the amount of carrier required for adsorbing unit dosage of optimized SNEDDS formulation. The oil adsorption capacity (OAD) of carriers should be high to get better flow and compaction. Gravimetric method was used to estimate OAD³⁵.

 

Characterization of Solid formulations:

Differential scanning calorimetry:

DSC thermograms of budesonide, Neusilin UFL2 and solid-SNEDDS formulation were obtained by heating the samples in an open aluminium pan from 35 to 450 ̊C at a scanning rate at 10 ̊C / min under the stream of nitrogen³⁶.

 

X-Ray diffractometer:

X-ray powder scattering measurements of budesonide and solid-SEDDS powder were carried out. The powder X-ray diffraction patterns were recorded at room temperature using monochromic CuKα-radiation (K= 1.5406 Å) at 40 mA and at 45 kV over a range of 2 θ angles from 3 ̊ to 50 ̊ with an angular increment of 0.02 ̊ per second³⁷.

 

Fourier transformed infrared spectroscopy:

FTIR Spectra of Neusilin UFL2, optimized S-SNEDDS were obtained using Diamond ATR spectrophotometer (Cary 630, Agilent Technologies, USA) and studied for the presence of characteristic peaks³⁸.

 

Micromeritic properties of Solid formulations:

Prepared solid-SNEDDS were evaluated for micromeritic properties such as angle of repose, bulk density, tapped density, Hausner’s ratio and Carr’s compressibility index^39,40,41.

 

Reconstitution properties of Solid formulations:

About 100 mg Solid-SNEDDS was accurately weighed and introduced into 100 ml distilled water in a beaker at 37 ̊C and gently mixed using magnetic stirrer at 100 rpm. Rapid emulsification was observed, when

§  Tendency to form an emulsion was determined as:

Good- if emulsification occurs in <1 min with clear (or) transparent emulsion.

Bad- if emulsion is less clear^42,43.

 

Drug content:

A 100 mg sample was dissolved in 10 ml buffer and filtered using 0.45 μm membrane filter. The content was estimated by UV method⁴³.

 

                                Practicalvalue

% Drugcontent= ––––––––––––––––– X100

                               Theoriticalvalue

 

In vitro drug dissolution studies of Solid formulations:

In vitro dissolution studies of S-SNEDDS were performed using USP dissolution test apparatus II (Electrolab India TDT 08L) in 900 ml buffer of 0.1 N HCl and pH 6.8 buffer at 37 ± 0.5 C with a paddle speed of 50 rpm.

 

 

Table 1: Solubility of budesonide in Oils, Surfactants and Co-surfactants

    *Values expressed as mean±S.D, n=3

Samples were withdrawn at 5, 10, 15, 20, 30, 45 and 60 min and replaced with fresh media. Samples were analyzed spectrophotometrically for budesonide at 245 nm in triplicate. Percentage of cumulative drug dissolution at different time intervals was calculated and a graph plotted versus time^44,45,46.

 

RESULTS:

Solubility studies:

To improve drug loading efficiency and reduce final volume of SNEDDS formulation this technique is important. The solubility of drug in individual system is given in Table 1. The maximum solubility was observed in span 80 and minimum solubility was observed in kolliphor RH 40.

 

 

Fig. 1: Ternary Phase diagram

 

Construction of ternary phase diagram:

From solubility studies, oils, surfactants and co-surfactants indicating highest solubility of budesonide were selected. Ternary phase diagram was constructed to find out the micro/nanoemulsion area⁴⁷. Ternary phase diagram where, surfactant: co-surfactant (1:1, 2:1) with an oil concentration of no more than 40% showed micro/ nano emulsion area than (1:2) in Fig.1. The size of micro/nano emulsion area depends upon the amount of water consumed in the titration. Therefore, for the preparation of SNEDDS formulation, Oil: S-Mix 1:9, 2:8 and 4:6 were selected from all the three ratios of surfactant: co-surfactant (1:1, 2:1 and 1:2) and 3:7 ratio were rejected due to phase separation observed after 72 h^9,10. The optimized formulations (1:9, 2:8, 4:6) were selected for incorporation of budesonide (9 mg).

 

Characterization of liquid formulations:

Self-Emulsification time and visual assessment:

The emulsification time is directly proportional to amount of oil phase and inversely proportional to S-Mix ratio. All the formulations       LF1, LF2, LF3 exhibited self-emulsification time 19.8, 16.4, 21.1 s respectively and no phase separation observed for the formulations.

 

Phase separation and drug precipitation study:

Uniform emulsion formation from SNEDDS is very important at different dilutions because drugs may precipitate at higher dilution in vivo which affects the drug absorption significantly. Hence each formulation LF1(1:9), LF2(2:8) and LF3(4:6) subjected to 10, 100, 1000 times dilution in water, 0.1N HCl, and pH 6.8 phosphate buffer, and there was no phase separation observed. However, formulation LF2 in 10 times dilution with phosphate buffer only shown phase separation.

 

Centrifugation test:

The formulations checked for evidence of phase separation or precipitation and all formulations passed the test as shown in Table 2.

 

Cloud point measurement:

At temperature higher than the cloud point, an irreversible phase separation occurs due to dehydration of its ingredients, which may affect drug absorption. Hence, to avoid this phenomenon, the cloud point for the SNEDDS formulation should be above body temperature, and the results ranged from 62 °C to 69 °C as shown in Table 2.

 

Percent transmittance:

A high value of transmittance is indicative of optical clarity of the system. Evaluated SNEDDS formulations showed transmittance values above 95% confirming micro/ nano emulsification efficiency of the SNEDDS given in Table 2.

 

Droplet size and PDI determination:

BUDESONIDE loaded SNEDDS formulations had the mean particle size in the range of 82.4 nm. The optimized formulation of SNEDDS shown PDI value of 0.349 indicating homogenous droplet population and narrow globule size distribution shown in Fig. 2(A).

 

Fig. 2: (A) Droplet size (B) Zeta potential

 

Table 2: Characterization of liquid formulations

 

Zeta potential:

The obtained zeta potential value of BUDESONIDE loaded SNEDDS optimized formulae F2 2:8 with drug were found to be –28.6 mV, indicating the stability of formulation with the drug shown in Fig. 2(B).

 

Drug content:

Drug content estimated for all the formulations and found to be in the range of 80% to 102% as shown in Table 2.

 

Turbidity measurement:

Turbidimetry results of all the formulations were in the range of 0.01 to 0.06 shown in Table 2.

 

Refractive index:

There was no significant difference in the values of refractive index for the formulations tested. The refractive index values close to that of the water (1.333) as shown in Table 2.

 

In vitro drug release of liquid formulations:

Dissolution studies were performed for the SNEDDS formulations in 0.1N HCl and phosphate buffer pH 6.8, and the results were compared with the pure drug Fig. 4 (a, b). There is no significant difference in dissolution of three SNEDDS formulations. As the emulsification time is below 25 s, about 100% of drug is released within 5 min in case of SNEDDS in pH 6.8 while pure drug showed only 19.9 % dissolution at the end of 5 min and 47.7% in 60 min. In 0.1 N HCl, the formulations released maximum 18%, 53.7% and 26.5% respectively in 60 min against pure drug release of 48.4%.

 

Preparation of budesonide loaded Solid-SNEDDS:

All conventional budesonide loaded L-SNEDDS formulations are ranked based on in vitro drug release, drug loading efficiency and self-emulsification time. LF2 formulation has shown the good results as given in the Table 3. When compared to other formulations, hence, it has been optimized for conversion into S-SNEDDS.

 

Table 3: Rank order of budesonide liquid formulations

(Numbers are as per the rank order).

 

Oil adsorption capacity:

Oil adsorption capacity of Neusilin UFL2 was found to be better as compared to other carriers used, viz., Neusilin US2 and Aerosil 200. The oil adsorption capacity of carriers found to be Neusilin UFL2 (190 mg) > Neusilin US2 (200 mg) > Aerosil 200 (210 mg).

 

Characterization of Solid Formulations:

Solid state characterization Techniques:

DSC studies:

The DSC of budesonide and Neusilin UFL2showed sharp endothermic peaks at 259.16 ̊C and 226.8 ̊C which correspond to melting point of the drug and the carrier respectively. The DSC of optimized Solid-SNEDDS of drug and excipients revealed negligible change in the melting points of budesonide and excipients, indicating that there is no interaction between the drug and the excipients used in the Solid-SEDDS shown in Fig. 3(a).

 

FTIR Spectroscopy:

The FTIR spectra are mainly used to determine interaction between the drug and any of excipients used⁴⁸. The presence of interaction is detected by the disappearance of the important functional group. The characteristic peak of pure budesonide at 3486.9, 2957.6, 1666.1, 889.0 are assigned due to stretching of O-H, C-H, C=O, C=C and C-H (aromatic rings) groups and are in confirmation with reported values for the drug. The characteristic peaks of Neusilin UFL2 in the fig 3(b) at 3492.5 and 993.3 were assigned due to O-H and Si-O and in conformity with reported values. Similar peaks were observed in tablet mixture of Solid-SNEDDS, along with absence of interfering peaks indicating there is no interaction between budesonide and other used excipients.

 

X-ray diffraction studies:

The X-ray diffractogram of pure budesonide clearly showed the peak indicating that the drug is in crystalline form, the peak intensity of Solid-SNEDDS indicating considerable reduction than the pure drug.  This marked reduction in peak intensities provides increase in dissolution rates of Solid-SNEDDS preparation shown in Fig. 3(c).

 

Fig. 3: Solid State Characterization 4(a) DSC 4(b) FTIR 4(c) XRD

 

Table 4: Micromeritic and reconstitution properties of Solid formulations

(Values expressed as mean±s.d., n=3)

 

Fig. 4: In-vitro drug release profiles of SNEDDS in liquid and solids a) 0.1 N HCl buffer L-SNEDDS b)6.8 pH phosphate buffer L-SNEDDS c) ) 0.1 N HCl buffer S-SNEDDS d) 6.8 pH phosphate buffer L-SNEDDS e) optimized formulation of both liquid and solid SNEDDS with  drug

 

Micromeritic and reconstitution properties of Solid formulations:

The values obtained for the angle of repose, Bulk density, Tapped density, Hausner’s ratio, Carr’s index shown in Table 4 indicate good acceptable flow and compressibility. For reconstitution properties a dilution study was done to observe the effect of dilution on S-SNEDDS, because dilution may better mimic the condition of stomach after oral administration. It was observed that the six S-SNEDDS formulations SF1 to SF6 disperse quickly and completely when subjected to an aqueous environment under mild agitation, results given in Table 4.

 

In vitro dissolution studies of Solid formulations:

The cumulative percent drug release from Solid-SNEDDS was found to be higher than that of pure drug as shown in Fig. 4. The drug release in case of pure drug was only 48.4% and 47.7% in 0.1 N HCl and 6.8 pH phosphate buffer respectively in 60 min. Budesonide release in 20 min from Solid-SNEDDS was found to be 101% and 102% for SF4 and SF6 respectively and for SF5 formulation shown 100% in 30 min in pH 6.8 buffer. The maximum percent drug release was 57.62% in 60 min in 0.1 N HCl with SF1.  The drug release study also indicates that the self-nanoemulsifying property of the formulation remains unaffected by the conversion of Liquid-SNEDDS to the Solid-SNEDDS form as illustrated in Fig. 4(c, d). It was also noticed that the release of budesonide from the S-SNEDDS was slightly lower than the Liquid- SNEDDS. This might be attributed to the presence of adsorbent material which may delay the dissolution rate to a small extent. These findings were also compatible with reported values.

 

It was found that the drug release profile of the Liquid-SNEDDS showed no significant differences when compared to those of Solid-SNEDDS Fig. 4 (e), suggesting that the SNEDDS preserve a similar performance in emulsification regardless of the form (i.e., liquid or solid).

 

DISCUSSION:

The present work was aimed to formulate Solid-SNEDDS using BCS class II drug budesonide involving pre solubilization. Capryol 90, tween 80 and propylene glycol were selected as oil, surfactant and co-surfactant phases from the solubility studies. Ternary phase diagram was constructed to identify nanoemulsion ratios of components. Capryol 90: Tween 80: propylene glycol (10: 45: 45), (20: 40: 40), (40: 40: 20) were selected and optimized based on the lowest oil concentration NMT 40 %¹⁴. Similar characterization techniques employed with glimepiride S-SNEDDS to optimize L-SNEDDS⁴⁹. In-vitro drug release profile has showed increase in dissolution with respect to emulsification time below 25 s. The emulsification is due to tween 80 which has high ability to reduce interfacial tension between O/W interfaces⁵⁰. L-SNEDDS formulation LF2 (2:8) optimized based on various characterization techniques and dissolution which released 100% in 5 min against pure drug release 47.7% in 60 min in 6.8 pH phosphate buffer. The optimized formulation LF2 (2:8) has droplet size 82.4 nm, PDI 0.349 and zeta potential -28.8 mV indicating stability and homogeneity of the nano particles¹⁷.To improve stability, optimized L-SNEDDS converted to Solid-SNEDDS by adsorption technique using carriers Aerosil 200, Neusilin US2 and Neusilin UFL2. Solid-SNEDDS evaluated for the solid-state characterization, reconstitution properties, pre and post compression parameters and in vitro drug release studies. As there are no significant changes in spectra of FTIR, XRD and DSC studies indicate no chemical interaction between the drug and excipients. In vitro drug release profile of Solid-SNEDDS tablets was compared with the pure drug in different dissolution media to evaluate the effects of pH on dissolution profile of the Solid-SNEDDS. The results indicate that drug release was in the range of 48.67% to 57.62% for all the formulations in 0.1 N HCl buffer in 60 min, whereas in 6.8 pH phosphate buffer formulations SF4 and SF6 showed 100% release in 20 min, SF5 showed 100% in 30 min and pure drug 47.7% in 60 min and formulation SF4 was optimized. In vitro release of optimized L-SNEDDS released 100% in 5 min whereas Solid-SNEDDS released 101% in 20 min. This may be due to presence of adsorbent material which may delay the dissolution rate to a small extent suggesting that the SNEDDS preserve a similar performance in emulsification regardless of the form (i.e., liquid or solid)⁴². However, the stability will be good for solid-SNEDDS. Neusilin ULF2 indicated excellent flow properties. Reconstitution properties of S-SNEDDS formulation SF4 with Neusilin UFL2 and CCS indicated better self-emulsification time 28 s, drug content of 99.89% and transmittance of 98.19%.

 

Self-nanoemulsifying drug delivery system is a vital tool in overcoming the formulation difficulties and improving solubility of hydrophobic/lipophilic drugs⁵¹. In this study, three individual components were selected from the solubility study and performed ternary ratios to obtain the best nanoemulsion region. From the obtained regions different characterization techniques were used to obtain best L-SNEDDS formulation. To improve the stability L-SNEDDS converted to S-SNEDDS. The optimized formulation showed good properties in both L-SNEDDS and S-SNEDDS. Novel technique of SNEDDS can be successfully applied to improve the solubility and dissolution rate of budesonide.

 

ACKNOWLEDGEMENT:

The authors are thankful to the management of Maharajah’s College of Pharmacy for the constant encouragement and support for doing this work. The authors also thankful to the management of M/s Avik Pharma Ltd., India for gratis supply of Budesonide.

 

CONFLICT OF INTEREST:

The authors declare that they do not have any conflict of interest.

 

ABBREVATIONS:

SNEDDS: Self-Nanoemulsifying drug delivery systems; L-SNEDDS: Liquid self-nano emulsifying drug delivery systems; S-SNEDDS: Solid self-nano emulsifying drug delivery system; FT-IR: Fourier transform infrared spectroscopy; DSC: Differential scanning calorimeter; PDI: Polydispersity index.

 

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Accepted on 31.12.2020           © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(11):5755-5763.