Background: Lovastatin is a statin drug used for lowering cholesterol in those with hypercholesterolemia to reduce the risk of cardiovascular disease. It is a BCS class II drug i.e. it has low aqueous solubility and high permeability.
Objectives: Improvement of solubility and in vivo efficacy was investigated by formulating binary solid dispersions.
Methods: Binary solid dispersions of lovastatin were formulated in the current study using two polymers i.e. Soluplus and PEG 4000. Seven batches of solid dispersions were prepared (S1, P1, SP1, SP2, SP3, SP4, and SP5) via the solvent evaporation method. The prepared dispersions were evaluated for equilibrium solubility, FTIR, XRD, DSC, SEM studies, and further in vitro drug release were evaluated. The results revealed significant enhancement in the solubility of drug-using polymer hybrids as compared to that of individual polymer dispersion batches.
Results: A significant solubility enhancement was observed with SP5 (approx 40 times) having a higher concentration of Soluplus. FTIR studies indicated no drug to polymer interaction. DSC studies revealed complete amorphization of polymer and also X-RD data is also in compliance with DSC results. In vitro drug release studies showed almost 100% release in 2h in polymer hybrid batches in comparison to individual polymer batch (S1 and P1). The best dissolution characteristics were observed in SP3 and SP5 which is also in compliance with solubility data. Further in vivo efficacy studies revealed a significant reduction in LDL, HDL, TG, AST, and ALT levels in comparison to pure drug lovastatin group and hypercholesterolemia control group.
Conclusion: Hybrid polymer may be a prospective carrier system for the enhancement of solubility of BCS class II drugs.
[http://dx.doi.org/10.2174/1567201811666140311103425] [PMID: 24611664]
[http://dx.doi.org/10.1016/j.ejpb.2012.12.018] [PMID: 23333900]
[http://dx.doi.org/10.1016/j.ijpharm.2015.03.079] [PMID: 25843761]
[http://dx.doi.org/10.1016/j.colsurfb.2014.07.037] [PMID: 25124835]
[http://dx.doi.org/10.1248/cpb.c14-00725] [PMID: 25832024]
[http://dx.doi.org/10.1016/j.ijpharm.2015.11.007] [PMID: 26581773]