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

Enteric coating of ibuprofen tablets (200 mg) using an aqueous dispersion system

Ibuprofen is a propionic acid derivative that belongs to the class NSAIDs. Major adverse reactions associated with Ibuprofen are related to GIT and include peptic and mucosal ulcers, dyspepsia, severe gastric pain and bleeding, that results in excessive treatment failure. The goal of this study was to develop enteric coated ibuprofen tablets in order to avoid gastric mucosal irritation, diffusion of drug across mucosal lining and to let active ingredient be absorbed easily in small intestine. The formulation was developed and manufactured through the direct compression process, the simplest, easiest and most economical method of manufacturing. Enteric coating was done using an Opadry white subcoating and an aqueous coating dispersion of Acryl-Eze. Enteric coated formulation was subjected to disintegration and dissolution tests by placing in 0.1 M hydrochloric acid for 2 h and then 1 h in phosphate buffer with a pH of 6.8. About 0.04% of drug was released in the acidic phase and 99.05% in the basic medium. These results reflect that ibuprofen can be successfully enteric coated in order to prevent its release in the stomach and facilitate rapid release of the drug in the duodenum, due to the presence of superdisintegrant. Formulating this enteric coated tablets could increase patient compliance by decreasing adverse drug reactions (ADR S) associated with Ibuprofen therapy.Ibuprofeno é um derivado do ácido propiônico, que pertence à classe dos fármacos não-esteróides (AINES). As principais reações adversas associadas com o ibuprofeno se referem àquelas do trato gastrintestinal (TGI), como úlceras pépticas e da mucosa, dispepsia, dor gástrica grave e sangramento, que resultam em muitas falhas de tratamento. O objetivo do estudo foi desenvolver comprimidos revestidos de ibuprofeno que impeçam a irritação da mucosa gástrica, difusão do fármaco através da mucosa e permitam, facilmente, a absorção do princípio ativo do intestino delgado. A formulação foi desenvolvida e manufaturada por meio de processo de compressão direta, método mais simples e econômico de preparação. O revestimento entérico foi efetuado utilizando-se subrevestimento com Opadry branco e revestimento por dispersão aquosa de Acryl-Eze. A formulação de revestimento para liberação entérica foi submetida a testes de desintegração e de dissolução, em ácido clorídrico 0,1 M, por 2 h, e, então, a h, em tampão fosfato pH 6,8. Cerca de 0,04% do fármaco foi liberado na fase ácida e 99,05%, no meio básico. Estes resultados refletem o fato de que o ibuprofeno pode ser revestido com sucesso, a fim de impedir sua liberação no estômago e facilitar a rápida liberação do fármaco no duodeno, devido à presença de superdesintegrante. A formulação de tais comprimidos aumentaria a adesão do paciente pela diminuição das reações adversas (RAs), associadas à terapia com ibuprofeno

Formulation development and optimization of cefuroxime axetil tablets by direct compression method and its stability studies

Cefuroxime axetil (CA) immediate release (IR) tablets were developed and optimized by direct compression method. Ten formulations were designed and optimized using central composite design with two main variables, microcrystalline cellulose PH 102 and croscarmellose. Pharmaceutical evaluation of the formulations was conducted emphasizing on dissolution profile of the drug by USP dissolution test using apparatus II in 0.07 N HCl and in medium of pH 1.2, 4.5 and 6.8 to determine the dissolution pattern of the low soluble drug. Test formulations were compared against reference brand using f2 similarity factor. Test formulations were assayed by a validated HPLC method, with acetonitrile and 10 mM ammonium acetate solution (pH = 5.2) in a ratio of 15:85 as mobile phase. Stability studies under stress were conducted on selected formulations according to ICH guidelines. It was conclusive that stable CA formulations could be developed by direct compression method.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development and evaluation of naproxen sodium 250 Mg effervescent tablets

Effervescent tablets have always been convenient, simple and measured dosage form. The phenomenon of carbonation, in this type of dosage form, accelerates the solubility and enhances the bioavailability of the drug and the addition of flavorant also masks the objectionable taste of the medicament in a more patient compliant way. The present study focuses on developing a new, simple, cost effective formulation of naproxen sodium 250 mg as an effervescent tablet using direct compression technique. Nine different trial formulations of naproxen 250 mg were designed with varying proportions of sodium carbonate, sodium bicarbonate, citric acid and PEG 6000 and were prepared by direct compression method, and evaluated for pharmaceutical quality attributes. Quality assessment proved formulations F8 as a satisfactory one showing respectively mean weight of 2200 ± 50.52 having hardness and friability of 14.78421 ± 1.3791 kg and 1.241 %. Tablets took 4 min and 36 s to disintegrate completely. The average pH of the solution was within the range of 5.65 to 5.85. Dissolution profile comparison with the conventional formulation was carried out and maximum drug release by the trial formulation was observed within 15 min. spectrophotometric determination of drug content was found to be 99.82 ± 1.754. Stability characterization was also conducted on the formulations under stress (40 °C/75 % R.H.) that showed formulations remained stable throughout the study duration with acceptable difference in physical and chemical characteristics. Such formulations increases patient compliance and have possibly improved bioavailability. The work also emphasizes on the benefit of using direct compression method as a cost effective technique in terms of process, materials handling with productivity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Pharmaceutical quality control studies on gatifloxacin 200 mg tablets available in the pakistani market

The aim of present work was to compare the quality of different brands of gatifloxacin 200 mg tablets, collected from different retail pharmacies in the local market of Pakistan. Five different brands were characterized by physical and chemical parameters such as, weight variation, hardness, thickness, friability, disintegration, dissolution, uniformity of contents and assay. Among them dissolution either single point or multiple point, including release profile comparison is most important tool for establishing the quality of the product. Brand A was considered as a reference because it passed all physical, chemical, quality control test and it was also brand leader, while brands B, C, D and E were test brands due to their production in local pharmaceutical. Quality control tests were satisfactory and within the limits for all test brands. The aim either biowaiver study of all the brands should conduct or not the similarity and difference among the brands were measured. Results revealed that brand B and D shown the best similarity with brand A and least differential value when we used the model independent f2 factor for similarity and f1 factor for difference. Model dependent methods Zero order, First order, Higuchi release model and Hixson-Crowell method were also used and shown the concentration dependent release of drug, i.e. first order kinetic. The results showed that model-dependent methods were more discriminative than model-independent method. A criterion for selecting the most appropriate model was based on linearity (coefficient of correlation).Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development of in vitro-in vivo correlation for nimesulide loaded ethylcellulose microparticles

A predictive in vitro-invivo correlation (IVIVC) can empower in vitro dissolution as a surrogate for in vivo bioavailability / bioequivalence. IVIVCs can decrease regulatory burden by decreasing the number of biostudies required in support of a drug product. The present study concerns the establishment of in vitro-in vivo correlation for three different sustained release nimesulide loaded ethylcellulose microparticulate formulations (M1, M2 and M3) and conventional tablet (100 mg Nimaran®-Novartis, Pakistan). In vitro dissolution study was conducted in phosphate buffer pH 6.8 stirred at 50 rpm and 37 ± 0.5ºC. A validated HPLC method was adopted to conduct bioavailability studies in young healthy human volunteers. Ultimately IVIVC of prepared microparticles and conventional tablet was established using Wagner-Nelson method. M1 and M2 formulations and Nimaran® exhibited good linear IVIVC (R2 = 0.9220, 0.9124, 0.8728, respectively) as compared to M3 (R2 = 0.9449). The results substantiate the success of this mathematical simulation study encourage researchers to conduct biowaiver studies for other BCS class II drugs.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum