Study On Benproperine Phosphate Sustained Release Pellets

The pellet-based multiple unit extended release dosage forms are gaining more importance as a result of their several advantages: they reduce the risk of systemic toxicity due to dose dumping, decrease local irritation , diminish peak plasma fluctuations and minimize potential side effects. Benproperine phosphate is an antitussive drug. The objective of this work was to develop a sustained release device for benproperine phosphate, producing in two steps, a pelletised formulation produced by centrifugal granulating process and coated with aqueous dispersion.In the study, high-performance liqul(?) chromatography methods were developed for in vivo and in vitro content assays Ultraviolct spectrophotomatry method was applied for drug release. Three methods had good precision and accuracy. The preformulation results showed that benproperine phosphate was easily soluble in water and various physiological pH fluids.Drug layered pellets based on mierocrystalline cellulose beads as substrates were prepared using a laboratory-scale centrifugal granulator. The effect of four independent process parameters (rotor rotation speed.feed powder rate, spray rate and balling time) on responses describing yield, roundness and (?)lability were studied using a orthogonal design. It was discovered that the yield of the objective pellets was about 80%. The result suggested that the preparation process and formulation of cllets can reach the expected goals.The pellets were coated by spraying (?) aqueous dispersion as film forming agent by a rotation coating processor. The coating f(?)(?)mulation composed of Eudragit? NE 30D were studied on coating level, anti-tacking agents. static electricity-proofing and curing time, etc. Clearly, the coating level influenced the benproperine phosphate release form coating pellets. A central composite design was used (?)(?)valuate the effect of the film thickness and concentration of lactose in the coating (?)(?)sion composed of Eudragit RL/RS30D on the drug release properties. The percent drug released during dissolution from the pellets was calculated from the actual drug content. A formulation was prepared under the optimized conditions yielding response values which were close to the predicted values. Visual examination of the fraction released versus time curve in the presence of the input data points corroborated with statistical data lead us to the conclusion that the square root of time model provided the best correlation. The Higuchi model appears to provide the best correlation.Stability studies of preparation were shown that light, temperature and moisture had little effect on self-made sustained releasepellets.The plasma concentration in six dogs was tested after a single oral administration of commercial tablets and self-made sustained release pellets. The pharmacokinetics parameters and the relative bioavailability were measured. The pharmacokinetics parameters of test formulation and reference formulation were/_max 4.3±1.4h and 3.3±1.5h, C_max 1.00±0.29 mg·mL^-1 and 1.02±0.29 mg·L^-1, AUC_0-T 12.15±3.95μg·h·L^-1 and 11.58±2.53μg·h·L^-1, respectively. The relative bioavailability of test formulation is 103.4%. The results indicated that it had satisfactory sustained release effect. Good correlation existed between absorption in vivo and dissolution in vitro.