Thiolated polymers: Stability of thiol moieties under different storage conditions

The purpose of this study was to evaluate the stability of thiolated polymers - so-called thiomers. A polycarbophil-cysteine conjugate and a chitosan-thioglycolic acid conjugate were chosen as representative anionic and cationic thiomer. The thiol group bearing compounds L-cysteine and thioglycolic acid were introduced to polycarbophil and chitosan, respectively with a coupling reaction mediated by a carbodiimide. The resulting thiolated polymers were freeze-dried and the amount of thiol groups on the thiomer was determined spectrophotometrically. Each kind of polymer was directly used or compressed into 1 mg matrix-tablets. Polymers were stored for a period of six months at four different storage conditions, namely at -20°C (56% relative humidity; RH), 4°C (53% RH), at 20°C (70% RH), and at 22°C (25% RH). Samples were taken after 6 months to determine the formation of disulfide bonds and the remaining thiol groups on the polymer. When the polycarbophil-cysteine and chitosan-thioglycolic acid conjugate were stored as powder a decrease of free thiol groups was observed only after storage at 20°C and 70% RH. Both polymers were found to be stable under all storage conditions when compressed into matrix tablets. The results provide the base for the use of thiomers as auxiliary agents in commercial products

Thiolated polymers: Stability of thiol moieties under different storage conditions

The purpose of this study was to evaluate the stability of thiolated polymers - so-called thiomers. A polycarbophil-cysteine conjugate and a chitosan-thioglycolic acid conjugate were chosen as representative anionic and cationic thiomer. The thiol group bearing compounds L-cysteine and thioglycolic acid were introduced to polycarbophil and chitosan, respectively with a coupling reaction mediated by a carbodiimide. The resulting thiolated polymers were freeze-dried and the amount of thiol groups on the thiomer was determined spectrophotometrically. Each kind of polymer was directly used or compressed into 1 mg matrix-tablets. Polymers were stored for a period of six months at four different storage conditions, namely at -20°C (56% relative humidity; RH), 4°C (53% RH), at 20°C (70% RH), and at 22°C (25% RH). Samples were taken after 6 months to determine the formation of disulfide bonds and the remaining thiol groups on the polymer. When the polycarbophil-cysteine and chitosan-thioglycolic acid conjugate were stored as powder a decrease of free thiol groups was observed only after storage at 20°C and 70% RH. Both polymers were found to be stable under all storage conditions when compressed into matrix tablets. The results provide the base for the use of thiomers as auxiliary agents in commercial products.</jats:p

Effect of Thiolated Polymers to Textural and Mucoadhesive Properties of Vaginal Gel Formulations Prepared with Polycarbophil and Chitosan

The aim of this study was to design and evaluate of mucoadhesive gel formulations for the vaginal application of clomiphene citrate (CLM) for local treatment of human papilloma virus (HPV) infections. Chitosan (CHI) and polycarbophil (PC) were covalently modified using the thioglycolic acid and L-cysteine, respectively. The formation of thiol conjugates of chitosan (CHI-TG) and polycarbophil (PC-CYS) were confirmed by FT-IR analysis and PC-CYS and CHI-TG were found to have 148.42 ± 4.16 and 41.17 ± 2.34 μmol of thiol groups per gram of polymer, respectively. One percent CLM gels were prepared by combination of various concentrations of PC and CHI with thiolated conjugates of these polymers. Hardness, compressibility, elasticity, adhesiveness and cohesiveness of the gels were measured by Texture profile analysis and the vaginal mucoadhesion was investigated by mucoadhesion test. The increasing in the amount of the thiol conjugates was found to enhance the elasticity, cohesiveness, adhesiveness and mucoadhesion of the gel formulations but not their hardness and compressibility when compared to gels prepared using their respective parent formulations. Slower release rate of CLM from gels was achieved when the polymer concentrations were increased in the gel formulations. PC and its thiol conjugate were found to prolong the release of CLM longer than 70 h unlike gel formulations prepared using CHI and its thiol conjugate which were able to release CLM up to 12 h. Stability of CLM was preserved during the 3 month stability analysis under controlled room temperature and accelerated conditions

A Comprehensive Development Strategy in Buccal Drug Delivery

This work combines several methods in an integrated strategy to develop a matrix for buccal administration. For this purpose, tablets containing selected mucoadhesive polymers loaded with a model drug (omeprazole), free or in a complexed form with cyclodextrins, and in the absence and presence of alkali agents were subjected to a battery of tests. Mucoadhesion studies, including simple factorial analysis, in vitro release studies with both model-dependent and model-independent analysis, and permeation studies were performed. Mucoadhesive profiles indicated that the presence of the drug decreases the mucoadhesion profile, probably due its hydrophobic character. In tablets loaded with the drug complexed with β-cyclodextrin or methyl-β-cyclodextrin, better results were obtained with the methylated derivative. This effect was attributed to the fact that in the case of β-cyclodextrin, more hydroxyl groups are available to interact with the mucoadhesive polymers, thus decreasing the mucoadhesion performance. The same result was observed in presence of the alkali agent (l-arginine), in this case due to the excessive hydrophilic character of l-arginine. Drug release from tablets was also evaluated, and results suggested that the dissolution profile with best characteristics was observed in the matrix loaded with omeprazole complexed with methyl-β-cyclodextrin in the presence of l-arginine. Several mathematical models were applied to the dissolution curves, indicating that the release of the drug, in free or in complexed state, from the mucoadhesive matrices followed a super case II transport, as established on the basis of the Korsmeyer–Peppas function. The feasibility of drug buccal administration was assessed by permeation experiments on porcine buccal mucosa. The amount of drug permeated from mucoadhesive tablets presented a maximum value for the system containing drug complexed with the methylated cyclodextrin derivative in presence of l-arginine. According to these results, the system containing the selected polymer mixture and the drug complexed with methyl-β-cyclodextrin in presence of l-arginine showed a great potential as a buccal drug delivery formulation, in which a good compromise among mucoadhesion, dissolution, and permeation properties was achieved