BCS Class II and IV Drug´s Solubilisation using Cycodextrin-PVP-PEG6000 Complexes through a Factorial Study Design

Abstract

Objective: Class II and IV drug on the Biopharmaceutical Classification System are those with the commonest solubility issues. The objective of this work is to study the effect of the use of cyclodextrin combined with each PVP, and PEG 6000 individually, then combined, and the enhancement of solubility and dissolution rate on three BCS class II celecoxib and Valsartan, and Class IV Furosemide. Methods: A serie of 23factorial experiments were conducted. Drug´s solubilities were assessed in eight selected fluids containing Beta Cyclodextrin, Polyvinylpyrrolidone and Poly Ethylene Glycol 6000 individually and in binary and ternary combinations. Solid inclusion complexes of each drug beta Cyclodextrin, Polyvinylpyrrolidone and Poly Ethylene Glycol 6000 were prepared by kneading method, to evaluation the impact of each excipient on dissolution rates per 23factorial design. Results: Solubility levels of the three studied drugs was highly enhanced by the studied excipients. The highest solubility improvement was recorded for the combination of ßCD with PEG 6000 (4,95ratio) IN THE CASE OF Celecoxib, and forß-CD in combination with PEG 6000 and PVP (25,52 ratio) in the case of FSD, then in the combination of ßCD with PEG 6000 (21, 41ratio) in the case of Valsartan. The highest enhancement of celecoxib dissolution rates was recorded for CCX-ßCD (1:2) - PEG 6000 (2%) combination (10,03 ratio), for FSD- ßCD (1:2)-PEG 6000 (2%)-PVP (2%) combination (22,61 ratio) in the case of furosemide and for VST-PVP (2%) combination (3,54ratio) in the case of Valsartan. Conclusion: PEG 6000 is a suitable solubilizer alone and in combination with ßCD and PVP to enhance the solubility and dissolution rate of the selected three BCS Class II and IV drugs.