Methods: The effects of independent variables (poloxamer 407 and hydroxypropyl methyl cellulose (HPMC) concentration) on various dependent variables (gelling capacity, pH and viscosity) were investigated by using 32 factorial design and organoleptic evaluation was done with descriptive analysis.
Results: The optimized formula of chloramphenicol in situ gel yielded 9 variations of poloxamer 407 and HPMC bases composition in % w/v as follows, F1 (5; 0.45), F2 (7.5; 0.45), F3 (10; 0.45), F4 (5; 0.725), F5 (7.5; 0.725), F6 (10; 0.725), F7 (5; 1), F8 (7.5; 1), F9 (10; 1). The results indicated that the organoleptic, pH, and gelling capacity parameters matched all formulas (F1-F9), however, the viscosity parameter only matched F3, F6, F8, and F9. Based on factorial design, F6 had the best formula with desirability value of 0.54, but the design recommended that formula with the composition bases of poloxamer 407 and HPMC at the ratio of 8.16 % w/v and 0.77 % w/v, respectively, was the optimum formula with a desirability value of 0.69.
Conclusion: All formulas have met the Indonesian pharmacopoeia requirements based on the physical evaluation, especially formula 6 (F6), which was supported by the result of factorial design analysis.
METHODS: By adding Hydroxy Propyl Methyl Cellulose (HPMC) as a precipitation inhibitor to conventional SNEDDS, a supersaturable system was prepared. Firstly, the prepared SNEDDS played an important role in increasing the aqueous solubility and hence oral absorption due to nano-range size. Secondly, the S-SNEDDS found to be advantageous over SNEDDS for having a higher drug load and inhibition of dilution precipitation of Dutasteride. Formulated S-SNEDDS (F1-F9) ranged from 37.42 ± 1.02 to 68.92 ± 0.09 nm with PDI 0.219-0.34 and drug loading of over 95 percent.
RESULTS: The study of in-vitro dissolution revealed higher dissolution for S-SNEDDS compared to SNEDDS and Avodart soft gelatin capsule as a commercial product. In addition, higher absorption was observed for S-SNEDDS showing approximately 1.28 and 1.27 fold AUC (0-24h) and Cmax compared to commercial products. Therefore, S-SNEDDS has proven as a novel drug delivery system with a higher drug load, higher self-emulsification efficiency, higher stability, higher dissolution and pronounced absorption.
CONCLUSION: In conclusion, S-SNEDDS could be a newly emerging approach to enhance aqueous solubility in many folds for drugs belonging to BCS Class II and IV and thus absorption and oral bioavailability.