Salivary stimulation by prolonged release of pilocarpine in sjõgren’ syndrome

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

The effect of different grades polymer blends on release profiles of diclofenac sodium from hydrophilic matrices.

An attempt was made to design matrix tablet of diclofenac sodium by using various grades of hydroxypropyl methyl cellulose (HPMC E50, E15 and E300LV). The effect of hydrophilic polymers was studied on release characteristics of the diclofenac matrix tablet. Dicalcium phosphate and magnesium stearate were used as an excipients. Tablets were prepared by direct compression method. The in vitro dissolution test carried out for 12 hrs using USP dissolution apparatus II at 50 rpm in 900ml phosphate buffer pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The tablet evaluation parameters of hardness, friability, thickness, content uniformity were founded within the limit. At a fixed polymer level, drug release from the higher viscosity grades E50 was slower as compared to the lower viscosity grades (E300LV and E15). Tablet prepared with HPMC E50 is more release retardant. As the drug to polymer ratio increased drug release decreased. The dissolution study revealed that maximum retardation of the drug was obtained by highest viscosity grade HPMC at higher concentrations. The release of the model drug from these HPMC matrix tablets was prolonged.

Evaluation of Cedrela gum as a binder and bioadhesive component in ibuprofen tablet formulations

The compressional, mechanical and bioadhesive properties of tablet formulations incorporating a new gum obtained from the incised trunk of the Cedrela odorata tree were evaluated and compared with those containing hydroxypropylmethylcellulose (HPMC). Compressional properties were evaluated using Hausner's ratio, Carr's Index, the angle of repose, and Heckel, Kawakita and Gurnham plots. Ibuprofen tablets were prepared using the wet granulation method. Bioadhesive studies were carried out using the rotating cylinder method in either phosphate buffer pH 6.8 or 0.1 M hydrochloric acid media. The gum is a low viscosity polymer (48 cPs), and Fourier transform infrared spectroscopy revealed the presence of a hydroxyl group. Py and Pk values, which are measures of plasticity, showed the gum to be significantly (p<0.05) more plastic than HPMC, and plasticity increased with polymer concentration. All tablet formulations were non-friable (<1.0%), and the formulations containing the gum had a higher crushing strength (130.95 N) than those containing HPMC (117.85 N) at 2.0% w/w binder. Formulations incorporating the gum were non-disintegrating and had a significantly longer drug release time than those containing HPMC. At the highest binder concentration, Cedrela gum formulations adhered to incised pig ileum longer than those containing HPMC. Cedrela gum exhibited better compressive, flow and binding properties than HPMC and is suitable as a bioadhesive and for sustained release of drugs.

Propriedades de compressão, mecânicas e de formulações de comprimidos bioadesivos, que incorporam nova goma de mascar obtidas a partir de incisão de tronco da árvore de Cedrela odorata, foram avaliadas e comparadas com aquelas contendo hidroxipropilmetilcelulose (HPMC). Propriedades de compressão foram avaliadas usando a razão de Hausner, índice de Carr, ângulo de repouso e os gráficos de Heckel, Kawakita e Gurnham. Prepararam-se comprimidos de ibuprofeno utilizando o método de granulação a úmido. Realizaram-se estudos de bioadesividade utilizando o método de cilindro rotativo em tampão fosfato pH 6,8, ou meio ácido com 0,1 M de ácido clorídrico. A goma é um polímero de baixa viscosidade (48 cPs) e a espectroscopia no infravermelho por Transformada de Fourier (FTIR) revelou a presença de um grupo hidroxila. Valores de Py e Pk, que são medidas de plasticidade, mostraram que a goma é significativamente (p <0,05) mais plástica do que HPMC e que a plasticidade aumenta com a concentração de polímero. Todas as formulações de comprimidos mostraram-se não-friáveis (<1,0%) e aquelas contendo a goma apresentaram maior resistência ao esmagamento (130.95N) do que aquelas contendo HPMC (117.85N) em 2,0% (p/p) do ligante. As formulações que incorporaram a goma eram não-desintegrantes e apesentaram tempo de liberação significativamente maior do que aquelas contendo HPMC. As formulações de goma de Cedrela aderiram à incisão de íleo de porco por tempo maior do que aquelas contendo HPMC com a maior concentração de ligante. A goma Cedrela apresentou melhor fluxo, compressão e propriedades de ligação do que HPMC e é adequada como bioadesivo e para a liberação sustentada de fármacos.

Avaliação da influência de adjuvantes não-poliméricos solúveis na liberação do nimodipino a partir de formulações matriciais de liberação prolongada / Evaluation of soluble non-polymeric adjuvants in the release of nimodipino from controlled release matrices formulations

Fármacos com características lipofílicas costumam apresentar velocidade de difusão muito baixa a partir de matrizes hidrofílicas de liberação, comprometendo a obtenção de níveis plasmáticos terapeuticamente efetivos. Contudo, a liberação de fármacos lipossolúveis a partir de sistemas matriciais é influenciada pelo pH do meio, que pode facilitar a formação de cargas na molécula, melhorando sua performance. O objetivo deste trabalho foi avaliar a capacidade de adjuvantes não poliméricos em facilitar a solubilização do Nimodipino, “in vitro”, através do perfil de dissolução de cápsulas matriciais de hidroxipropilmetilcelulose (HPMC). As formulações desenvolvidas apresentaram o mecanismo de liberação do fármaco pela matriz governado pelo processo de erosão de acordo com o modelo cinético de Korsmeyer-Peppas, onde n>1. Entretanto algumas formulações apresentaram 0.5> n < 1 demonstrando ser um sistema anômalo dependente de difusão e erosão. Os perfis de dissolução nos dois meios testados mostraram-se distintos podendo observar diferenças significativas entre eles.

Drugs with slow solubility present very low diffusion from hydrophilic matrices, committing the serum levels therapeutically effectives. However, the liberation of lipophilic drugs starting from matrix systems is influenced by the pH of the medium, that it can facilitate the formation of charges in the molecule, improving your performance. The objective of this work was to evaluate the capacity of non-polymeric excipients in facilitating the solubilization of Nimodipino “in vitro”, through the capsules dissolution profiles of hydroxypropylmethylcellulose matrices. The developed formulations presented the release mechanism of drug influenced by erosion process according with the kinetic model of Korsmeyer-Peppas, where n>1. However, some formulations presented 0.5> n <1 demonstrating to be an anomalous system dependent of diffusion and erosion. The dissolution profiles in the two tested mediums showed different, allowing to observe significant differences among them.

Influence of cellulose polymers type on in vitro controlled release tablets containing theophylline

In this study, the effect of ethylcellulose (EC) and 6 types of hydroxypropylmethylcellulose (Methocel® K100M, K100MPRCR, K15MPRCR, K4MPRCR, K4M PR and E4MCR) on release profile of theophylline from matrix tablets was evaluated. Formulations tablets were prepared by either wet granulation or direct compression technique. The tablets were evaluated for physical characteristics and in vitro release of drug was performed as described in USP 30 ed. (Test 3). All formulations with cellulose polymer produced tablets easily and with physicals characteristics in accordance with official limits. Drug dissolution tests showed that formulations with 15 percent of Methocel® K4MPR, 15 percent of Methocel® K4MPRCR and 30 percent of Ethocel® N10STD, obtained by direct compression method, complied with official specifications, in terms of release profile and diffusion was the main mechanism involved in theophylline delivery.

Os efeitos das variáveis das formulações na liberação da teofilina a partir da hidroxipropilmetilcelulose (HPMC) e etilcelulose (EC) em comprimidos matriciais foram estudados. Formulações de comprimidos foram preparadas pelos métodos da granulação úmida ou compressão direta usando diferentes viscosidades de HPMC. Propriedades físico-químicas dos comprimidos e liberação do fármaco foram estudadas conforme dissolução descrita no Teste 3 da Farmacopéia Americana 30ed. Ensaios "in vitro" mostraram que as formulações com 15 por cento de Methocel® K4MPR, 15 por cento de Methocel® K4MPRCR e 30 por cento de Ethocel® N10STD obtidas por compressão direta apresentaram bom perfil de liberação de teofilina e a difusão foi o principal mecanismo envolvido na liberação.

Influence factors of the release rate of benorilate from sustained-release matrix tablets / 第三军医大学学报

Objective To study the influence factors of the release rate of benorilate from sustained release matrix tablets. Methods The matrix tablets of benorilate were prepared by using hydroxypropylmethylcellulose (HPMC) as the matrix material. The effects of the contents of HPMC, polyvinyl pyrrolidone (PVP), and microcrystaline cellulose (MCC), and the method of preparation on in vitro drug release were studied by evaluating the n value in the Peppas equation. Results The increasing HPMC content led to decrease of benorilate release. However, PVP and MCC used in this experiment accelerated the benorilate release from the tablets. The drug released from the tablet prepared by dry method was faster than that by wet method. Conclusion The contents of HPMC, PVP, and MCC, especially HPMC, have effects on the release rate of benorilate, but the two preparation methods have less effect.

Preparation of Sustained-Release Tetramethylpyrazine Phosphate Tablet and its Bioavailability on Rabbits / 复旦学报（医学版）

Purpose To prepare the sustained-release tablet of tetramethylpyrazine phosphate with hydroxypropylmethylcelluose(HPMC) as matrix material. MethodsThe paddle method and the HPLC method were erspectively used determined the cumulative drug released in vitro and the serum concentration in vivo.ResultsThe cumulative drug released in the first hour was about 20%, while in 12 hours it was above 85%. Drug release behavior can be best described by Higuchi equation, and the release rate decreased as the viscosity and/or the amount of HPMC increased. Compared with the market tablet on the rabbits, the sustained release tablet had the decreased peak concentration (P < 0.05 ); the prolonged peak time and mean residence time (P< 0.05).ConclusionsThe matrix tablet was a good sustained-release dosage form and it had a good in vitro-in vivo correlation.