Estudo da liberação in vitro de progestagênios em diferentes formas farmacêuticas usados para suporte da fase lútea no tratamento de infertilidade
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2011-05-30
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Universidade Federal de Goiás
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INTRODUCTION: The dissolution profile of a drug is an important tool for evaluating its biopharmaceutical quality. The pharmaceutical form must be guaranteed to release the appropriate quantity of the drug at the appropriate rate to assure that the therapeutic objective of the product, which is directly related to its bioavailability, will be achieved. In order to permit interchangeability between medications, quality, safety and efficacy must first be guaranteed. Failure to comply with these conditions may result in therapeutic failure. OBJECTIVES: To evaluate the dissolution profile of the principal pharmaceutical forms of progestogens available on the market in Brazil for luteal phase support in infertility treatment. METHODS: A laboratory study was developed and conducted in the Pharmaceutical Technology Laboratory of the School of Pharmacy, Federal University of Goiás (UFG). The following formulations were evaluated: coated tablets of dydrogesterone, micronized progesterone in the form of soft gelatin capsules produced by two different pharmaceutical companies (product A and product B) and a gel form. The study also included suppositories and ovules from three compounding pharmacies. Evaluation was made using physical and physicochemical tests and in vitro release assays. In the case of the pharmaceutical preparations in the form of soft gelatin capsules, dissolution kinetics and dissolution efficacy were also determined in addition to the profile of the preparation. The products with the same pharmaceutical form were compared. Different equipment, a dissolution apparatus equipped with an Enhancer Cell assembly and Franz diffusion cells, were tested and also compared in an attempt to determine the best method of evaluating semisolid forms. Statistical analysis was performed using the SPSS statistical software program for Windows, version 16.0. ANOVA, the Tukey test and Student s t-test were used in the comparative analysis. RESULTS: Evaluation of dydrogesterone in the pharmaceutical form of coated tablets showed the product to be in accordance with pharmacopeial specifications. The tablets were approved in the first stage of the dissolution assay, drug dissolution being above 85% at 60 minutes for all the units tested. With respect to the dissolution profile of the three batches of the micronized progesterone products evaluated (products A and B), in the form of soft gelatin capsules from different pharmaceutical companies, drug dissolution within 4 hours was 80%, i.e. all the products met the established dissolution specifications. The dissolution profiles and first-order kinetics of products A and B, which consisted of micronized progesterone in the form of soft gelatin capsules, were similar. The dissolution apparatus equipped with an Enhancer Cell assembly was found to constitute the best means of characterizing the rate and extent of release of the drug in gel form from its matrix. The in vitro release assay for micronized progesterone in the form of soft gelatin capsules conducted in the dissolution apparatus confirmed the prolonged release mechanism of the drug, which lasted for up to 72 hours. None of the ovules or suppositories from any of the compounding pharmacies evaluated met the criteria established by the regulatory agencies and official compendia with respect to the quality requirements for drugs. The dissolution profile differed between batches and between the different pharmacies investigated. Mean maximum concentrations of micronized progesterone failed to exceed 80% of the dose stated on the label. Statistically significant differences were found between batches originating from the same pharmacy and between the different pharmacies investigated. CONCLUSIONS: It was impossible to establish the interchangeability of the reference products with the compounded products tested. Further bioavailability studies and randomized clinical trials should be conducted to test the different products with the best performance in the dissolution studies conducted.
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FINOTTI, Marta Curado Carvalho Franco. Release in vitro study of different pharmaceutical forms of progestogenes used in luteal support treatment of infertility. 2011. 150 f. Tese (Doutorado em Ciencias da Saude) - Universidade Federal de Goiás, Goiânia, 2011.