| Phentermine is a kind of adrenergic drugs that act on the central nervous system and stimulate release or blocking the reuptake of norepinephrine. Phentermine play its function for the treatment of obesity by causing norepinephrine ending failure, further suppress appetite, reduce food intake, thereby reducing the patient’s weight.Topiramate have the effect of weight loss may be due to increase the patient’s sense of satiety with weakened gastrointestinal movement and improve the degree of boredom of taste, and reduce the heat energy intake, etc. The compound formulation of phentermine and topiramate can play a good synergy. Phentermine play a very good curative effect that can quickly be absorbed in the body, which because of quick-release. But topiramate can compensate the drug reduced that due to phentermine blood drug concentration decreased as a sustained-release formulation. It reduces the drug dosage and ADRs. In this paper the studies of before prescribing mainly researches on the basic properties of active pharmaceutical ingredients, such as melting point, hygroscopicity, solubility, logP and pka. Phentermine hydrochloride and Topiramate is a kind of single crystal type of drugs, both are white powder and the melting point of203℃,126℃, respectively. Phentermine have slightly hygroscopicity, and easily soluble in water.,but topiramate almost have no hygroscopicity, soluble in water and easily soluble in ethanol. The research provides support for later use and store drugs. The paper established the method for determining the content and the release of active pharmaceutical ingredients and preparations, including phentermine given priority to HPLC-UV chromatography analysis method and topiramate with HPLC-refractive index detection analysis method. In the study, to prepare PTM quick-release pellets and TPM sustained-release pellets by Glatt fluid bed coating mechanism. The preparation of quick-release pellets to make the drug solution layered inertia sugar cores. The preparation technology was determined by the single factor investigation to choose atomization pressure of1.5bar, inlet air temperature of60℃. On the concentration of the solution is20%. The structure of sustained-release pellets from inside to outside is sucrose blank pill core, take medicine and sustained-release coating layer. It is the method of Hassan to prepare quick-release pellets, with indexes of particle size distribution, roundness, brittle broken degrees, hygroscopicity, the medicine rate and the fluidization state. The optimization of the formulation including the solvent of60%ethanol and the solution concentration was40%. Research of the preparation for sustained-release pellets found that the main factors influencing the drug release include pore ratio, coating weight and coating liquid mixing time. Using the method of multi-target full probability evaluation method and the orthogonal experiment to design the best prescription of preparing sustained-release pellets that coating weight gain of6%, the pore system of29.5%, solution mixing time for more than12h. Through the study of investigating drug release of pellets under the external environment(high temperature, high humidity, illumination) and different conditions found that TPM sustained-release pellets release stably from the outside and release conditions change and change. To prepare the compound capsule contain PTM7.5mg and TPM46mg.The qua research of compound PTM-TPM double release capsule from identification, content uniformity, the difference of weight, the dissolution/release degree, content and related substances, etc. The results of the identify research show the main peak retention time of each sample is consistent with the reference substance. The result showed that containing hydrochloric acid phentermine and topiramate amount of95.0%～105.0%of each batch samples. With reference to appendix X E of Chinese pharmacopoeia (2010edition), examined of content uniformity test, the result shows that each batch of samples meet the requirements. The experiment to check the weight difference of large, medium and small size samples, showed each of batch of samples are comply with the relevant requirement of Chinese pharmacopoeia (2010edition). According to the results between each bath sample6grain dissolution/release behavior uniformity is good. And that each batch of samples phentermine HCL dissolution more than80%in10minutes. The cumulative release quantity in1,4,8hours of topiramate: shall be respectively corresponding to25%of the labeled amount below,60to85%and more than95%. To establish relevant material check method, the results of various specifications of the samples had no miscellaneous quality inspection.The compound preparation has the following features, such as ideality in vitro release, stability of drug release, the preparation process simple and reproducible, it will be for obese patients. |
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