Quality evaluation of simvastatin compounded capsules

Abstract

Simvastatin is commercially available as tablets and compounded capsules in Brazil. Very few reports regarding these capsules' quality, and consequently their efficacy, are available. The pharmaceutical quality of 30 batches of 20 mg simvastatin capsules from the market was evaluated by weight determination, content uniformity, disintegration (Brazilian Pharmacopeia), assay and dissolution test (USP32 tablet monograph). A HPLC method was developed for assay, content uniformity and dissolution test, and specifications were also established. Out of the 30 batches evaluated, 29 showed capsule disintegration within 45 min and individual weight variation was within ±10% or ±7.5% relative to average weight, for ≤ or > 300 mg, respectively. Only 27 batches met dissolution test criteria with values ≥80% of the labeled amount in 45 min; 21 batches showed simvastatin content between 90.0-110.0% of the labeled amount and 19 batches had at least 9 out of 10 capsules with content uniformity values between 85.0-115.0% of the labeled amount with RSD≤6.0%. Only 14 of all (30) batches fully met pharmacopeial quality standards. The establishment of test conditions and specification parameters for simvastatin capsules showed that there are relevant pharmacopeial quality differences between batches compounded by different pharmacies. For 53.33% of the tested products hypercholesterolemic treatment efficacy may be compromised. Uniterms:Compounded simvastatin capsules. Quality control. RP-HPLC.No Brasil, a sinvastatina está comercialmente disponível na forma de comprimidos e cápsulas manipuladas. Poucos relatos estão disponíveis sobre a qualidade e, consequentemente, a eficácia dessas cápsulas. A qualidade de 30 lotes de sinvastatina 20 mg cápsulas do mercado foi avaliada através da determinação de peso, uniformidade de conteúdo, desintegração (Farmacopéia Brasileira), doseamento e teste de dissolução (monografia comprimidos USP32). Método por CLAE foi desenvolvido para o doseamento, uniformidade de conteúdo e teste de dissolução; além disso, especificações foram estabelecidas. Dos 30 lotes avaliados, 29 apresentaram desintegração da cápsula até 45 min e a variação do peso individual foi ± 10% ou ± 7,5% em relação ao peso médio, se ≤ ou > 300 mg, respectivamente. Apenas 27 lotes preencheram os critérios do teste de dissolução com valores ≥ 80% da quantidade rotulada, em 45 min, 21 lotes apresentaram conteúdo de sinvastatina entre 90,0-110,0% do valor rotulado e 19 lotes apresentaram pelo menos 9 em 10 cápsulas, com valores de uniformidade de conteúdo entre 85,0 -115,0% da quantidade rotulada com RSD ≤ 6,0%. Apenas 14 de todos os lotes (30) atenderam completamente os padrões de qualidade farmacopéicos. O estabelecimento das condições para os testes e de especificações para os parâmetros das cápsulas de sinvastatina mostrou que houve diferenças relevantes na qualidade farmacopeica entre os lotes das cápsulas manipuladas por distintas farmácias. A eficácia do tratamento hipercolesterolêmico poderia estar comprometida para 53,33% dos pro...

Untitled

“…The results obtained from the study revealed that all the brands passed the general standard specifications for dissolution rate test for conventional release tablets. The difference in the result can be correlated to all factors which affect the dissolution rate from the raw material (purity) which can affect solubility, and all diluents which were used in the formulation of each brand [27][28][29][30] . The results obtained from the assessment of the percentage content of active ingredient in the four brands showed that all brands gave values within the specification which is average weight content between 95-105% of Simvastatin 31 .…”

A Novel Stability Study of Simvastatin Generic Tablet in Public Pharmacy Facilities of Purwakarta District, Indonesia

“…The UV analysis was done based on the method described by Kulkarni et al (Kulkarni et al, 2012) and Marques-Marinho et al (Marques-Marinho et al, 2011). The validation of the method was conducted as below.…”

“…In another study from Brazil, only 14 out of 30 batches of simvastatin 20 mg capsules were found to comply with pharmacopeia quality standards (Marques-Marinho et al, 2011) and 6 out of 18 simvastatin 40 mg capsules had an assay content of between 4 -87% (Markman et al, 2010). As Brazil has a tropical climate with hot and humid weather, this could be an important factor that influences the stability of the tablets during storage (Bott & Oliveira, 2007).…”

Cellulose and Its Derivatives Use in the Pharmaceutical Compounding Practice

“…For example, using a high percentage (30% w/w) of CMC-Na (anionic polymer) as a diluent in the compounding of capsules of simvastatin has a deleterious effect. These capsules showed serious drug release problems in pharmaceutical tests because they did not disintegrate or dissolve at all [83]. In this case, CMC-Na should have been used as a capsule disintegrating agent at a much inferior concentration (< 6%) [12].…”