Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f 2) results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.O objetivo do presente estudo foi desenvolver matriz de de tizanidina de liberação controlada. As formulações foram projetadas usando o método do componente, central com a ajuda de software Design expert(r), versão 7.0. Utilizou-se Avicel pH 101, no intervalo de 14-50%, como material de preenchimento, enquanto HPMC K4M e K100M, no intervalo de 25-55%, Etilcelulose 10 ST e 10FP, no intervalo de 15-45% e Kollidon SR, na faixa de 25-60% foram utilizados como agentes de liberação controlada, no planejamento de formulações diferentes. Vários parâmetros físicos, incluindo o fluxo de pó para as misturas e variação de peso, espessura, dureza, friabilidade, tempo de desintegração e liberação in vitro, foram testados para comprimidos. Ensaios dos comprimidos foram, também, realizados, tal como especificado em USP 35 NF 32. Avaliaram-se os parâmetros físicos de ambos, mistura em pó e comprimidos, como índice de compressibilidade, ângulo de repouso, variação de peso, espessura, dureza, friabilidade, tempo de desintegração e de ensaio, considerando-os satisfatórios para as formulações K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 e KSR9. O estudo de dissolução in vitro foi realizado em 900 mL de HCl 0,1 N, tampão de fosfato pH 4,5 e meio 6,8, usando aparelho USP II. Os perfis de liberação in vitro indicaram que as formulações preparadas com Ethocel 10 padrão não foram capazes de controlar a liberação do fármaco, enquanto as formulações K4M2, K100M9, E10FP2e KSR2, com teor de polímero variando entre 40 e 55% apresentaram padrão de liberação controlada de fármaco no meio anteriormente mencionado. Observou-se cinética de liberação de fármaco de ordem zero para as formulações K4M2 , K100M9, E10FP2 e KSR2. Resultados do teste de similaridade (f 2) para K4M2, E10FP2 e KSR2 foram comparáveis com a formulação de referência K100M9. Gráficos de superfície de resposta também avaliaram o efeito da variável independente sobre as respostas. Estudo de estabilidade foi realizado conforme as diretrizes do ICH e a vida de prateleira calculada foi de 24-30 meses para as formulações K4M2, K100M9 e E10FP2

Validation of patients’ satisfaction regarding medications’ information questionnaire (Psmiq) in Karachi, Pakistan

SUMMARY. The aim of present study was to develop a validated patient satisfaction regarding medications’ information questionnaire (PSMIQ). It was an extra cultural adaptation of previous questionnaires used in other part of the world. The PSMIQ was premeditated by an expert group of 15 physicians and 15 pharmacists from a formerly validated questionnaire. A preliminary draft of PSMIQ comprised of seventeen items, with responses recorded on a five Likert scale. The internal validation of PSMIQ was approved by conducting a cross-sectional and analytical study. Around one thousand and fifty patients participated in present study. The validity of PSMIQ items was determined through factor analysis, and the reliability was evaluated with Cronbach’s alpha coefficient (α). Cronbach alpha value for transformed 13-item questionnaire was found to be 0.738. These items were assigned four sub scales. When compared it was observed that these subscales were significantly correlated with one another (p < 0.01). Patient satisfaction level for items regarding general information and usage instructions was above 70% however their satisfaction regarding potential problems and cost issues was less than 40%. Their satisfaction was positively associated with females for subscale 1 and 4 (p < 0.01). Responders who were stable had better total satisfaction scores compared with unstable ones in response to subscale 1, 2 and 3. In response to item regarding potential problematic issue, hypertension patients were 1.687 times more satisfied than patients suffering from other diseases (OR = 1.687; 95% CI = 1.247-2.283). Patient satisfaction survey used in the present study was found to be reliable and valid. Respondents were more satisfied regarding medications’ general information and usage instructions, however not satisfied with information regarding potential problems and cost issues

Determination of Chemical Stability of Various Famotidine Dosage Forms by UV –Visible Spectrophotometric Method and Data Analysis by R-GUI Stability Software

H2 receptor antagonists are still the first line of therapy in treating gastro esophageal reflux diseases as well as other ulcers of the upper gastrointestinal tract. Accelerated stability studies of different brands of Famotidine tablets (20mg) and suspension(10mg/5ml),both liquid and dry, were carried out at 40 oC ± 2 oC (Temperature) and 75% R.H. ± 5% R.H. The assay of tablets was conducted by both HPLC and UV/Visible Spectrophotometric methods whereas for suspensions only UV/Visible Spectrophotometric method was used. The tests were conducted at 0, 1, 3 and 6 months as per guidelines of ICH for accelerated studies. The results of physical tests indicated that the dissolution of tablet decreases in all cases with time whereas disintegration of all brands was found within 15 minutes throughout the course of study while the hardness demonstrated to be decline with time. Kinetic treatment to determine rate constants and shelf lives indicated that dry suspension was more stable than liquids while the tablets showed stability for three years which was parallel to their claimed expiry. Among tablets, brand A was the most stable and among suspensions, brand C showed the longest stability. The stability studies were also carried out by using a software R-Gui (version 2.13) and results were compared with manually calculated results

Development and Validation of a HPLC Method for Determination of Pefloxacin in Tablet and Human Plasma

Objective(s)Developing and validating a simple, efficient, reproducible and economic reversed phase high performance liquid chromatographic (RP-HPLC) method for the quantitative determination of pefloxacin in bulk material, tablets and in human plasma. Materials and MethodsA shim-pack CLC-ODS column and a mobile phase constituting acetonitrile: 0.025 M phosphoric acid solution (13:87 v/v, pH 2.9 adjusted with KOH) were used. The flow rate was 1 ml/min and the analyses performed using ultraviolet (UV) detector at a wavelength of 275 nm using acetaminophen as an internal standard.ResultsThe developed method showed good resolution between pefloxacin and acetaminophen. It was selective to pefloxacin and able to resolve the drug peak from internal standard and from formulation excipients. The percentage of coefficient variation (CV) of the retention times and peak areas of pefloxacin from the six consecutive injections were 0.566% and 0.989%, respectively. The results showed that the peak area responses are linear within the concentration range of 0.125 µg/ml-12 µg/ml (R2= 0.9987). The limits of detection (LOD) and limits of quantitation (LOQ) for pefloxacin were 0.03125 µg/ml and 0.125 µg/ml. The intra-day and inter-day variation, RSD were 0.376-0.9056 and 0.739-0.853 respectively; also, inter-day variation with relative standard deviation (RSD) were 0.1465-0.821 in plasma. The accuracy results of 70%, 100%, and 130% drugs were 100.72%, 100.34%, and 100.09%, respectively.ConclusionThe method is linear, quantitative, reproducible and could be used as a more convenient, efficient and economical method for the trace analysis of drug in biological fluids, in raw material and tablets