Design and Evaluation of Extended Release Formulations of Some Anti Viral Drugs

Abstract

The anti-HIV drugs, stavudine, lamivudine and nevirapine are currently administered as conventional or extended release tablets with stavudine and lamivudine in fixed dose combination and nevirapine as separate formulation; however current regimen attracts poor compliance and adherence to therapy resulting in poor control of HIV infection. The present study aimed to develop sandwiched osmotic pump tablet (SOPT) for simultaneous and extended delivery of stavudine, lamivudine and nevirapine with a view to overcome the above said dis-advantages. Initially, elementary osmotic pump tablets (EOPTs)having all the three drugs stavudine, lamivudine and nevirapine; EOPTs with stavudine and lamivudine together and EOPTs having nevirapine alone were developed and evaluated for physicochemical and release characteristics as a prelude to design the sandwiched osmotic pump tablets (SOPTs).Based on the performance of EOPTs, the SOPTs were designed by two approaches with stavudine, lamivudine and nevirapine distributed equally in both the compartments as the first approach and the second approach having stavudine and lamivudine (soluble drugs) in one compartment and nevirapine (sparingly soluble) in the other compartment. The SOPTs included a middle push layer containing polyethylene oxide (PEO, mol.wt.6,00,000 gm/mol) as the expandable hydrogel. We studied the effect of PEO and potassium chloride (osmogen) in variable concentrations and variable orifice diameter on the release rate of the drugs. SOPTs developed by both approaches released the drugs with zero-order release of the drugs for 24 hours independent of pH and agitation intensity. The invivo bio-availability of the drugs from the developed SOPT was ascertained by correlating the in-vitro release data and in-vivo predictions. The results of the study Suggest that SOPT is beneficial for simultaneous and extended delivery of stavudine, lamivudine and nevirapine with improved patient adherence to the HIV therapy as compared to currently available dosage forms.