Key Formulation Considerations of Push-Pull Osmotic Pump (PPOP) Drug Delivery System / 中国药学杂志

ABSTRACT

OBJECTIVE: Push-pull osmotic pump (PPOP) is one of conventional osmotic pump systems, which has been widely investigated for formulation development of BCS Ⅱ APIs. However, there is still a lack of experimental data based discussions for some key formulation factors of PPOP. Thus, to investigate some key formulation factors by designed experiments and tried to give some recommendations for those considerations in industrial formulation development. METHODS: Nifedipine was selected as the model drug in this study. The hydration & swell rate and strength of three grades of commercialized high molecular weight polyethylene oxide (PEO) were evaluated via swelling volume change using a home-made apparatus and via compression force using texture analyzer, respectively. The effect of different film coating thickness, proportion of osmotic agent in push layer, and ratios of push layer to pull layer were investigated by drug dissolution using USP apparatus Ⅱ as well. RESULTS: The swelling rate and strength of three grades of high molecular weight PEO (POLYOXTM 301, POLYOXTM Coagulant, and POLYOXTM 303) enhanced along with the molecular weight. The difference of swelling rate is not significant (P>0.05), but that of swelling gel strength is significant (P<0.05). Adding osmotic agent, e.g. NaCl, could significantly improve the swelling rate. Thicker coating membrane retarded drug release and as the coating thickness was higher than 180 μm, it caused incomplete drug release (<90%). When the NaCl proportion in push layer was between 10% and 30 %, there was no significant differences among drug dissolution profiles. However, when the percent of NaCl content in push layer was above 50%, the drug release from PPOP became slower and more incomplete (<90%). CONCLUSION: The ratio of DL/PL has significant impact on drug release. The lower the ratio of DL/PL resulted in faster and more complete drug release. For nifedipine case, the ratio of 2 was recommended.