Floating tablets of hydralazine hydrochloride: optimization and evaluation

Abstract

Hydralazine hydrochloride has a half-life of 2 to 4 hours with an oral bioavailability of 26-50%. Since hydralazine has a demethylating effect on various suppressor genes, it can be used in various types of cancer to support chemotherapy. The purpose of this study was to optimize and evaluate floating tablets of hydralazine hydrochloride designed to prolong the gastric residence time and to provide controlled release of the drug for 14 h. The floating tablets of hydralazine hydrochloride were prepared by the wet granulation method. Semi-synthetic polymers of hydroxy propyl methyl cellulose (HPMC K100M) and ethyl cellulose were used as the release retarding agents. A 2 2 factorial design was applied to systematically optimize the drug release profile. The concentrations of HPMC K100M and ethyl cellulose were optimized to provide controlled release of hydralazine for 14h. Non-Fickian diffusion release transport was confirmed as the release mechanism for the optimized formulation and the predicted values agreed well with the experimental values. Drug excipient compatibility studies were investigated by FTIR, DSC and XRD. These data indicate that there were no chemical interactions between the drug and the polymer. In vivo X-ray imaging showed floating tablet performance in rabbits.Uniterms: Hydralazine/floating tablets/evaluation. Hydralazine/floating tablets/optimization. Hydralazine/floating tablets/controlled release. In vivo X-ray/tablets performance. Cancer/treatment. O cloridrato de hidralazina apresenta meia-vida de 2 a 4 horas, com biodisponibilidade oral de 26-50%. Uma vez que a hidralazina possui efeito desmetilante em vários genes supressores, ela pode ser utilizada para diversos tipos de câncer, em apoio à quimioterapia. O objetivo deste estudo foi o de avaliar e otimizar comprimidos flutuantes de cloridrato de hidralazina, planejados para prolongar o tempo de residência gástrica e proporcionar liberação controlada do fármaco por 14 h. Os comprimidos flutuantes de cloridrato de hidralazina foram preparados pelo método de granulação úmida. Polímeros semi-sintéticos de hidroxipropiletil celulose (HPMCK100M) e acetato de celulose foram utilizados como agente de retardamento de liberação. Aplicou-se planejamento fatorial 2 2 para otimizar sistematicamente o perfil de liberação do fármaco. As concentrações de HPMCK100M e de etilcelulose foram otimizadas para se obter liberação controlada de hidralazina durante 14 h. O transporte de liberação de difusão não-Fickiana foi confirmado como o mecanismo de liberação para a formulação otimizada e os valores previstos estiveram de acordo com os valores experimentais. Estudos de compatibilidade entre fármaco e excipiente foram realizados por FTIR, DSC e DRX. Estes dados indicaram que não havia interação química entre o fármaco e o polímero. Imagens de raios-X in vivo mostraram o desempenho dos comprimidos flutuantes em coelhos.Unitermos: Hidralazina/comprimidos flutuantes/avaliação. Hidralazina/comprimidos flutuantes/ otimização. Hidralazina/comprimidos flutuantes/lib...

Formulation and in Vitro Evaluation of Amlodipine Gastroretentive Floating Tablets Using a Combination of Hydrophilic and Hydrophobic Polymers

“…3 ) whereas floating lag time decreases with increasing amount of sodium bicarbonate [37]. The carbon dioxide generated is widely relative to the quantity of sodium bicarbonate (NaHCO3) in the tablet.…”

Hydralazine HCl rapidly disintegrating sublingual tablets: simple dosage form of higher bioavailability and enhanced clinical efficacy for potential rapid control on hypertensive preeclampsia

“…Results of DSC studies are shown in Figures 1 and 2 . The DSC thermogram of HHC showed a broad endothermic melting peak at about 277.6°C; 29 – 31 this peak was retained in the same position with less intensity in physical mixture sample with d -Mannitol ( Figure 1B ), Pharmaburst ( Figure 2A ), and Saccharin ( Figure 2C ) due to drug dilution within the mixture. In case of drug physical mixture with SSG ( Figure 1C ), the drug melting peak was also retained with appearance of other sharp melting exothermic peak at 234°C.…”

The Influence of Wet Granulation Parameters on the Compaction Behavior and Tablet Strength of a Hydralazine Powder Mixture

“…Mughal et al [ 9 ] used the technique of extrusion and spheronization to produce hydralazine pellets. Vanitha et al [ 10 ] and Acharya et al [ 11 ] in their work dealt with the optimization and evaluation of floating tablets of hydralazine hydrochloride from granules created using wet granulation, designed to prolong the gastric residence time and to provide controlled release of the drug. Tablets must have a suitable mechanical strength to prevent chipping or breaking at manipulation, while ensuring adequate disintegration.…”