Studies On Key Technologies Of Aqueous Coating For Osmotic Pump Controlled-Release Dosage Forms

The purpose of this thesis was to improve the industrialization situation of osmotic pump dosage forms in China so that more osmotic pump products can be launched onto the market.Main works of this thesis were focused on the resolution or simplification of the limiting step in the manufacture process of osmotic pump,coating technique.The pH-independent aqueous coating materials were screened for osmotic pump through investigating the physicochemical properties of free films.Single layer osmotic pump tablets(OPTs)of water-soluble and push-pull osmotic pump tablets(PPOPs)of water-insoluble model drugs with different doses were prepared,and the release mechanisms of these two kinds of novel osmotic pump were studied in this thesis.The free films of four kinds of pH-independent aqueous coating materials which have the potential to applying on osmotic pump were prepared by casting method,added with different plasticizers.The water absorption and erosion,water vapor transmission coefficient(WVTc)and mechanical properties of cast films were investigated.The research results showed that Eudragit RL/RS 30D and Kollicoat SR 30D were more suitable for osmotic pump,comparing to Aquacoat ECD;Diacetin and TEC were more suitable as plasticizer for the aqueous coating of osmotic pump.In the case that Aquacoat ECD couldn't against the expansibility created by the core of osmotic pump during releasing,it wasn't appropriate for the aqueous coating of osmotic pump.Three different dose water-soluble drug,Betahistine HCl(1.5 mg),Propranolol HCl(PNH,40 mg)and Metformin(500 mg)were chosen as model drugs to prepare single layer osmotic pump by Eudragit RL/RS 30D and Kollicoat SR 30D,the effect of formula,coating process and curing process on drug release from aqueous coated osmotic pumps were studied.Preliminary stability results showed that the aqueous coated osmotic pumps were instable under the high temperature and high humidity conditions,as them stable under strong illumination.The deep research on the release mechanisms of Eudragit RL/RS 30D and Kollicoat SR 30D coated single layer osmotic pump demonstrated that drug release were driven by both osmotic pressure and diffusion,but the osmotic pressure was the main force.Three different dose water-insoluble drug,Indapamide(1.5 mg),Gliclazide(30 mg)and Etodolac(400 mg)were chosen as model drugs to prepare PPOPs by Eudragit RL/RS 30D,the effect of formula,coating process and curing process on drug release from aqueous coated osmotic pumps were studied.Preliminary stability results showed that the aqueous coated osmotic pumps were instable under the high temperature and high humidity conditions,as them stable under strong illumination.The deep research on the release mechanisms of Eudragit RL/RS 30D coated PPOPs demonstrated that the main force of drug release was driven by both osmotic pressure.Kollicoat SR 30D was not suitable for PPOPs.Using self-made conventional PPOPs as reference,relative bioavailability,pharmacokinetic study of aqueous coated PNH osmotic pumps(Eudragit RL/RS 30D-coated ones and Kollicoat SR 30D-coated ones)and aqueous coated Gliclazide osmotic pumps(Eudragit RL/RS 30D-coated ones)were performed in six beagle dogs by three-circle and two-circle crossover designs,as well as the in vitro and in vivo correlation,drug concentration in plasma of beagle dogs after single dose oral administered of osmotic pumps was detected by HPLC method.The results showed that tested preparations and referenced preparations were bioequivalent.The in vivo drug absorption rate of the dosage form has a direct relationship with the in vitro drug release rate of formulation.And all the in vivo drug absorption fraction of novel aqueous coated osmotic pumps had a high correlation with the in vitro drug release rate.