Formulation of gastroretentive floating drug delivery system using hydrophilic polymers and its in vitro characterization

O objetivo da presente pesquisa é o de formular e avaliar o sistema de liberação de fármaco gastrorretentivo flutuante, contendo o anti-hipertensivo, cloridrato de propranolol. Comprimidos gastrorretentivo flutuantes (GRFT) foram preparados utilizando um polímero hidrofílico sintético, o óxido de polietileno, de diferentes graus, tais como GE WSR N-12 K e GE 18 NF, como polímeros de retardamento de liberação, e carbonato de cálcio, como agente gerador de gases. Os GRFT foram comprimidos por compressão direta e avaliados para determinação das propriedades físico-químicas, flutuabilidade in vitro, estudos de inchamento, de dissolução in vitro e de mecanismo de liberação. Dos testes de dissolução e de flutuabilidade, selecionou-se F 9 como formulação otimizada. A formulação otimizada seguiu cinética de ordem zero, com mecanismo de difusão não-Fickiano. Essa formulação foi caracterizada por estudos de FTIR, não se observando interação entre o fármaco e os polímeros.The aim of the present research is to formulate and evaluate the gastroretentive floating drug delivery system of antihypertensive drug, propranolol HCl. Gastroretentive floating tablets (GRFT) were prepared by using a synthetic hydrophilic polymer polyethylene oxide of different grades such as PEO WSR N-12 K and PEO 18 NF as release retarding polymers and calcium carbonate as gas generating agent. The GRFT were compressed by direct compression strategy and the tablets were evaluated for physico-chemical properties, in vitro buoyancy, swelling studies, in vitro dissolution studies and release mechanism studies. From the dissolution and buoyancy studies, F 9 was selected as an optimized formulation. The optimized formulation followed zero order rate kinetics with non-Fickian diffusion mechanism. The optimized formulation was characterised with FTIR studies and observed no interaction between the drug and the polymers

Assessment of Hupu Gum for its Mucoadhesive Property in the Design and Evaluation of Mucoadhesive Buccal Patches of Propranolol HCl

ABSTRACT Objectives: There are no reports about assessment of the mucoadhesive property of formaldehyde treated hupu gum (HG). Hence the present study was undertaken to assessment of its mucoadhesive property of hupu gum in design of mucoadhesive buccal patches of Propanolol Hcl as a model drug. Methods: The prepared mucoadhesive buccal patches were compared with known muccoadhesive polymer, such as polyethylene oxide N 750. Poloxamer 407 is used as a penetration enhancer. The various physicomechanical parameters such as weight variation, folding endurance, thickness, surface pH, drug content, swelling studies and various ex vivo mucoadhesion parameters like mucoadhesive strength and force of adhesion were evaluated. In vitro diffusion studies as well as ex vivo drug release studies were performed. Results and conclusion: The results of the present investigation concluded that the formaldehyde treated hupu gum used as mucoadhesive polymer in development of buccal patches of propranolol Hcl were prepared by solvent casting method. Hupu gum is highly viscous, difficult to form buccal patches, due to this reason it is exposed to formaldehyde for 1hr to reduce its swelling nature. However, the variation in the release profile of propranolol Hcl due to different in the drug to polymer ratio. Finally, concluded that the formaldehyde treated hupu gum used as a mucoadhesive polymer

PREPARATION AND EVALUATION OF DROTAVERINE HCL ORAL DISINTEGRATING TABLETS USING SOLID MIXTURE TECHNIQUE

Objective: The objective of this study is to formulate orally disintegrating taste masked tablets of drotaverine HCl using solid mixture technique.Methods: Taste masked drug-polymer solid mixtures of drotaverine HCl were prepared by using hydroxypropyl methylcellulose (HPMC) 3 cps and rxcipient® FM1000/calcium silicate (rxcipient) as carriers employing kneading method using varying drug-polymer ratios of 1:1, 1:5, 1:7.5, and 1:9. Prepared drug-polymer mixtures evaluated for taste masking, and the ratio of drug-polymer is optimized. The granules and tablets prepared with optimized drug-polymer ratio were evaluated for pre- and post-compression parameters, in vitro dissolution studies, Fourier-transformation infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD) studies.Results: The drug:polymer ratios 1:7.5 with rxcipient and 1:9 with HPMC were optimized based on taste evaluation. The pre-compression results showed that all the formulae have good flow properties. The post-compression evaluations showed that all the formulae met the specifications of orally disintegrating tablets. From all the prepared taste masked drotaverine HCl tablets, R10 formulation consisting of 4% croscarmellose sodium and H9 formulation consisting of 3% croscarmellose sodium, 3% sodium starch glycolate, and 2% microcrystalline cellulose shown more than 99% drug release in 60 min, and both the formulations showed better taste masking and were meting oral disintegrating tablet (ODT) parameters. The optimized formulation was characterized by FTIR, DSC, and XRD studies and found no incompatibility.Conclusion: The results demonstrated that the prepared drotaverine HCl ODT showed better taste masking and meeting the parameters of ODT formulations R10 and H9. The present solid mixture technique can be effectively used for taste masking

DEVELOPMENT AND EVALUATION OF GASTRIC FLOATING TABLETS OF RIBOFLAVIN USING BOX-BEHNKEN DESIGN

Objective: To develop and evaluate gastric floating tablets of riboflavin that was thermally fused using an experimental design method. Methods: Gastric floating tablets were developed using the Box-Behnken design. The effect of sintering on various tablet properties is assessed. The prepared floating tablets were tested for characteristics like usual tablet quality control tests with special emphasis on buoyancy studies and in vitro drug release studies. Results: The drug-excipient incompatibility studies indicated no interactions between riboflavin and carnauba wax. Sintering the powder at 1200°C partially decreased its crystallinity and improved drug release for up to 16 hours. The tablets demonstrated good flow properties, acceptable hardness, low friability, and uniformity in thickness and diameter. Statistical models successfully optimized the formulation to achieve desired characteristics and practical compressibility. The optimal amounts of the variables according to Design Expert® 12 software were 59.19 mg of carnauba wax, 14.63% w/w of sodium bicarbonate, a sintering temperature of 74.68°C, and a sintering exposure time of 1.99 hours. Conclusion: In vitro dissolution studies were conducted on the optimized formulation to verify the model's predictions. The experimental results closely matched the predictions. The optimized formulations showed a floating lag time of 104 seconds and a floating duration of 12.3 hours. The obtained T90 was found to be 11.3 hours which followed zero order kinetics with a non-Fickian diffusion mechanism

Design and evaluation of lornoxicam bilayered tablets for biphasic release

The objective of the present investigation was to develop bilayered tablets of lornoxicam to achieve biphasic release pattern. A bilayered tablet, consisting of an immediate and controlled release layer, was prepared by direct compression technique. The controlled release effect was achieved by using various hydrophilic natural, semi synthetic and synthetic controlled release polymers such as xanthan gum, hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) to modulate the release of the drug. The in vitro drug release profiles showed the biphasic release behavior in which the immediate release (IR) layer containing the lornoxicam was released within 15 minutes, whereas the controlled release (CR) layer controlled the drug release for up to 24 h. All the bilayered tablets formulated have followed the zero order release with non-Fickian diffusion controlled release mechanism after the initial burst release. FTIR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 24 h from optimized formulations was observed. Based on the release kinetic parameters obtained, it can be concluded that xanthan gum polymer was suitable for providing a biphasic release of lornoxicam.<br>O objetivo do presente trabalho foi desenvolver comprimidos bicamada de lornoxicam para atingir padrão de liberação bifásica. Preparou-se, por compressão direta, comprimido bicamada, consistindo de uma camada de liberação imediata e uma de liberação controlada. A liberação controlada foi obtida pelo uso de vários polímeros naturais hidrofílicos, semi-sintéticos e sintéticos, tais como goma xantana, hidroxipropilmetil celulose (HPMC) e óxido de polietileno (PEO) para modular a liberação do fármaco. Os perfis de liberação in vitro mostraram comportamento bifásico em que a camada de liberação imediata (IR) contendo lornoxicam foi liberada em 15 minutos, enquanto a camada de liberação controlada (CR) liberou o fármaco em mais de 24 horas, Todos os comprimidos bicamada formulados seguiram a liberação de ordem zero com mecanismo de liberação controlada por difusão não fickiana após a liberação inicial por erupção. Os estudos de FTIR revelaram que não há interação entre o fármaco e os polímeros utilizados no estudo. A análise estatística (ANOVA) não mostrou diferença significativa na quantidade acumulada de fármaco após 15 minutos de liberação, mas observou-se diferença significativa (p<0,05) na quantidade de fármaco liberado após 24 h nas formulações otimizadas. Com base nos parâmetros de cinética de liberação obtidos, pode-se concluir que a goma xantana foi adequada para se atingir liberação bifásica de lornoxicam

Statistical design and evaluation of a propranolol HCl gastric floating tablet

The purpose of this research was to apply statistical design for the preparation of a gastric floating tablet (GFT) of propranolol HCl and to investigate the effect of formulation variables on drug release and the buoyancy properties of the delivery system. The contents of polyethylene oxide (PEO) WSR coagulant and sodium bicarbonate were used as independent variables in central composite design of the best formulation. Main effects and interaction terms of the formulation variables were evaluated quantitatively using a mathematical model approach showing that both independent variables have significant effects on floating lag time, % drug release at 1 h (D1 h) and time required to release 90% of the drug (t90). The desired function was used to optimize the response variables, each with a different target, and the observed responses were in good agreement with the experimental values. FTIR and DSC studies of the statistically optimized formulation revealed there was no chemical interaction between drug and polymer. The statistically optimized formulation released drug according to first order kinetics with a non-Fickian diffusion mechanism. Evaluation of the optimized formulation in vivo in human volunteers showed that the GFT was buoyant in gastric fluid and that its gastric residence time was enhanced in the fed but not the fasted state

Wound healing synergy in Wistar albino rats via green synthesized nanoparticles and topical antibiotic neomycin

Raise of antimicrobial resistance and lack of development in novel antibiotics leads to complications in infection control for wound healing. In perspective to search for best alternatives, antibacterial activity of nanomaterials has shown promising strategy, however concentration dependent toxicity became challenge thereof. In this context, green synthesis protocols of nano materials provide benefits of biocompatibility due to presence of bioactive compounds and also economical with proven efficiency. Further nano-antibiotic combinations may enhance antibacterial efficacy by synergetic action and allows to reduce the dosage of both agents. In the current work, nano-antibiotic gels are prepared using green synthesized nanoparticles (Ag &amp; ZnO NPs) with the combination of antibiotic neomycin and also assessed in-vivo wound healing activity on Wistar albino rats. From the results of the tested formulations, combinational formulations exhibited enhanced and speedier wound contraction (92–96%) with prominent synergetic action when compared with neomycin alone (84%) or nanoparticles alone (82–86%) in a 14-day study. These results demonstrated that green-nano-antibiotic combinational formulations provides prominent avenue to combat the multi drug resistant bacteria without toxicity issue

Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles

<p>Fisetin (FST), a potent anticancer phytoconstituent, exhibits poor aqueous solubility and hence poor bioavailability. The aim of the present study is to improve the oral bioavailability of FST by encapsulating into PLGA NPs (poly-lactide-co-glycolic acid nanoparticles) as a complex of HPβCD (hydroxyl propyl beta cyclodextrin) and to assess its anti-cancer activity against breast cancer cells. FST-HPβCD inclusion complex (FHIC) was prepared and the supramolecular complex formation was characterized by FTIR, DSC, PXRD and ¹H NMR. FHIC encapsulated PLGA nanoparticles (FHIC-PNP) were prepared and were studied for <i>in vitro</i> anticancer activity, cellular uptake, apoptosis and reactive oxygen species generation in MCF-7 human breast cancer cells. Comparative bioavailability of FST was determined after oral administration in C57BL6 mice as pure FST and FHIC-PNP. The results revealed that FHIC-PNP not only enhanced the anti-cancer activity and apoptosis of FST against MCF-7 cells but also improved its oral bioavailability, as demonstrated by increased peak plasma concentration and total drug absorbed.</p