Methods of synthesis of hydrogels … A review

AbstractHydrogels are being investigated recently for the bioactive molecules (in particular pharmaceutical proteins) controlled release, such as matrices, and for the living cells encapsulation. Biodegradable nature of hydrogels has created much interest for drug delivery systems. The original three-dimensional structure disintegrates into nontoxic substances to ascertain an excellent biocompatibility of the gel. Chemical cross-linking is the highly resourceful method for the formation of hydrogels having an excellent mechanical strength. Cross-linkers used in hydrogel preparation should be extracted from the hydrogels before use due to their reported toxicity. Physically cross-linked methods for preparation of hydrogel are the alternate solution of cross-linker toxicity

Chemically cross-linked poly(acrylic-co-vinylsulfonic) acid hydrogel for the delivery of isosorbide mononitrate.

We report synthesis, characterization, and drug release attributes of a series of novel pH-sensitive poly(acrylic-co-vinylsulfonic) acid hydrogels. These hydrogels were prepared by employing free radical polymerization using ethylene glycol dimethacrylate (EGDMA) and benzyl peroxide (BPO) as cross-linker and initiator, respectively. Effect of acrylic acid (AA), polyvinylsulfonic acid (PVSA), and EGDMA on prepared hydrogels was investigated. All formulations showed higher swelling at high pHs and vice versa. Formulations containing higher content of AA and EGDMA show reduced swelling, but one with higher content of PVSA showed increased swelling. Hydrogel network was characterized by determining structural parameters and loaded with isosorbide mononitrate. FTIR confirmed absence of drug polymer interaction while DSC and TGA demonstrated molecular dispersion of drug in a thermally stable polymeric network. All the hydrogel formulations exhibited a pH dependent release of isosorbide mononitrate which was found to be directly proportional to pH of the medium and PVSA content and inversely proportional to the AA contents. Drug release data were fitted to various kinetics models. Results indicated that release of isosorbide mononitrate from poly(AA-co-VSA) hydrogels was non-Fickian and that the mechanism was diffusion-controlled

Development and in vitro characterization of 5-flurouracilloaded, colon-targeted drug delivery system

Purpose: To prepare chondroitin sulphate–polyvinyl alcohol cross-linked microcapsules (miCAPs) for controlled delivery of 5-flurouracil (5-FU) in cancer patients.Method: Nine different miCAP formulations were prepared using emulsion cross-linking procedure. The formulations were evaluated for their physicochemical properties, complex formation, stability at variable temperatures, safety, as well as drug-loading and drug-release characteristics. The effects of glutaraldehyde (GA), polymer concentration and stirring speed on 5-FU release at various pH were also assessed.Results: One of the miCAP formulations (miCAP-1) was adjudged the most suitable based on its particle size, high drug loading (75.3 %, p = 0.034), and high entrapment efficiency (85.2 %, p = 0.031). Best-fit drug release model was Higuchi model based on regression coefficient value (R2) while drug release mechanism was Fickian.Conclusion: Highly stable, crosslinked, amorphous and drug delivery system has been successfully developed. The delivery system is potentially suitable for acid-sensitive therapeutic moieties and where controlled release is desired.Keywords: Emulsion cross-linking, Colon-specific delivery, 5-Flurouracil, Glutaraldehyde, Kinetic model

pH-sensitive polyvinylpyrrolidone-acrylic acid hydrogels: Impact of material parameters on swelling and drug release

In this study, we fabricated pH-sensitive polyvinylpyrrolidone/acrylic acid (PVP/AA) hydrogels by a free-radical polymerisation method with variation in the content of monomer, polymer and cross-linking agent. Swelling was performed in USP phosphate buffer solutions of pH 1.2, 5.5, 6.5 and 7.5 with constant ionic strength. Network structure was evaluated by different parameters and FTIR confirmed the formation of cross-linked hydrogels. X-ray crystallography showed molecular dispersion of tramadol HCl. A drug release study was carried out in phosphate buffer solutions of pH 1.2, 5.5 and 7.5 for selected samples. It was observed that swelling and drug release from hydrogels can be modified by changing composition and degree of cross-linking of the hydrogels under investigation. Swelling coefficient was high at higher pH values except for the one containing high PVP content. Drug release increased by increasing the pH of the medium and AA contents in hydrogels while increasing the concentration of cross-linking agent had the opposite effect. Analysis of the drug release mechanism revealed non-Fickian transport of tramadol from the hydrogels.Nesse estudo, preparamos hidrogéis de polivinilpirrolidona/ácido acrílico(PVP/AA), sensíveis ao pH, por meio de método de polimerização de radical livre, com variações no conteúdo de monômero, de polímero e de agente de ligação cruzada. O inchamento foi realizado em soluções tampão fosfato USP pH 1,2, 5,5, 6,5 e 7,5, com força iônica constante. A estrutura reticular foi avaliada por diferentes parâmetros e o FTIR confirmou a formação de hidrogéis de ligação cruzada. A cristalografia de raios X mostrou dispersão molecular do cloridrato de tramadol. Realizou-se estudo de liberação do fármaco em soluções tampão fosfato pH 1,2, 5,5 e 7,5 para amostras selecionadas. Observou-se que o inchamento e a liberação do fármaco dos hidrogéis podem ser modificados mudando-se a composição e o grau de ligação cruzada dos hidrogéis em estudo. O coeficiente de inchamento foi alto em pH mais altos, exceto para um deles com alto conteúdo de PVP. A liberação do fármaco aumentou com o aumento do pH do meio e do conteúdo em AA nos hidrogéis, enquanto que o aumento na concentração do agente de ligação cruzada apresentou efeito oposto. A análise do mecanismo de liberação do fármaco revelou transporte não Fickiano do tramadol dos hidrogéis

Development and release kinetics of a novel formulation of nimesulide prepared by microencapsulation using synthetic polymers

The synthetic polymers and their combinations were employed to retard the release of nimesulide from microcapsules. Microcapsules were prepared in different ratios of Eudragit RL 100 and hydroxy propyl methyl cellulose (HPMC) separately and in combination. All formulations of microcapsules were compressed to tablets. Dissolution of microcapsules and their tablets was performed by USP-apparatus-II in 900 mL borate buffer of pH 8.4 at 37.0 ± 0.5 ºC, at 50 rpm. In vitro kinetics was determined by various models including Zero order, First Order, Higuchi, Korsmeyer-Peppas and Hixson-Crowell. Eudragit showed higher retarding effect over extended period of time on release of drug than HPMC alone or its combination with Eudragit.Colegio de Farmacéuticos de la Provincia de Buenos Aire

ACCELERATED STABILITY STUDIES OF FLURBIPROFEN FILM COATED TABLETS OF FIVE DIFFERENT NATIONAL BRANDS IN PAKISTAN

Flurbiprofen is a potent non-steroidal anti-inflammatory drug, prescribed commonly for musculoskeletal and joint disorders like arthritis. It is well established that drug degradation during storage and transportation is of particular issue in tropical countries like Pakistan, having areas with temperature variations from 0oC (Muree, Islamabad, Sawat and Azad Jammu Kashmir) to 50oC (Sibi, Jackababad, Nawabshah, Larkana, Multan and Bahawalpur) and some areas with high relative humidity (Karachi). Present study was designed to evaluate five different national brands of flurbiprofen 100 mg film coated tablets by accelerated stability studies and examined for the parameters of hardness, disintegration, dissolution and assay for drug concentration in formulation after one, three and six months duration at controlled tropical conditions of temperature and relative humidity. Dosage forms of all selected national brands were found stable even after expiry date

Controlled-Release Low Density Effervescent Floating Matrix Tablets of Risperidone: Development, Optimization, in vitro-in vivo Evaluation in Healthy Human Volunteers and Determination of Dissolution Equivalency: Formulation and evaluation of floating matrix tablet of Risperidone in human volunteer

The main objective of the present study was to formulate gastroretentive effervescent sustained release drug delivery systems of risperidone floating tablets with the help of Methocel® K15, Ethocel® standard 7FP premium, Eudragit ® RS100 sustained release polymers to improve its safety profile, bioavailability and patient compliance. Risperidone floating tablets were formulated by wet granulation technique by using citric acid and sodium bicarbonate as a gas generating agent. Methocel® K15, Ethocel® standard 7FP premium, Eudragit® RS 100 were used to formulate floating effervescent sustained release tablets. Preliminary trials were done to investigate matrix integrity and floating behavior. On the basis of preliminary trials, various formulations were designed to optimize the best formulation. The FDA recommended statistical approach was used to test dissolution equivalency. Preliminary studies showed better floating behavior, but poor matrix integrity with Methocel®K15 containing formulations. Moreover, Ethocel® standard 7FP premium and Eudragit® RS 100 containing formulations showed better matrix integrity but poor floating behavior. Formulations RSFTIII, RSFTVI, RSFTIX were optimized and showed the drug release for 10 hours. Dissolution equivalency was tested for optimized formulation and found equivalent. In vivo-study also showed gastric retention time more than 4 hours