Studies On Osmotic Pump Controlled Release Preparations Of Allopurinol

In this paper, water-insoluble allopurinol with large dose was selected as a model drug to prepare bi-layer osmotic pump tablets (BOPT) and mono-layer osmotic pump tablets (MOPT). Then, pharmacokinetic study of allopurinol bi-layer osmotic pump tablets was performed in six beagle dogs.In the preparation of allopurinol BOPT, polyethylene oxide (PEO) and sodium chloride were used as the tablet core. Cellulose acetate (CA) and polyethylene glycol 2000 (PEG 2000) were selected as the coating materials and acetone was employed as the coating medium. According to drug release mechanism of BOPT, formulation of drug layer, push layer, coating membrane, preparation of tablet core and the condition of drug release were investigated to discuss the effects of different kind of factors on the release behavior of BOPT. Similarity factors (f₂) was used as the evaluation standard. Based on single-factor experiments, the amount of NaCl in drug layer, the content of PEG 2000 in coating membrane and coating thickness were selected as the causal factors, the synthetical mark was used as the evaluation standard to optimize the formulations according to orthogonal experiment design. The results indicated that the optimal formulation had the excellent zero-order release character and reproducibility of different batches. Comparison and analysis were carried out between the optimal formulation and conventional BOPT formulation of water- insoluble drug with small dose to widen the applicable dose scope of BOPT.In order to settle the time-lag and simplify the producing process of BOPT, allopurinol MOPT was also studied. The effects of some influencing factors on drug release were investigated, including the kind and quantity of PEO, the quantity of NaCl, the content of PEG 2000 in coating membrane, coating thickness and drug releasing orifice size .Orthogonal experiment design was used to optimize formulations. The optimal formulation had zero-order release character, and its drug release was almost complete. The mechanism of the drug release was discussed simply.With the commercial common allopurinol tablet as the reference, the pharmacokinetics study of self-prepared allopurinol BOPT was performed in six Beagle dogs. With two-preparation and two-period crossover design, HPLC was employed to detect the plasma...