However, swelling ratio of hydrogels at pH 1.2 might be due to protonation of amino groups and carboxylate ions present in the N-succinyl chitosan. These amino groups were less in number and swelling ratio was low. The composition of hydrogels had also influence on the swelling ratio. SP1, SP2, and SP3 hydrogels showed higher swelling due to less concentration of GA. Swelling ratio decreased with the increase in the concentration of GA.
The rate of drug release depends on the rate of penetration of dissolution fluid to the matrix which in turn depends on the porosity, the presence of hydrophobic additives and the wettability and particle surface. By coating of individual drug particles or granules by a slowly dissolving polymeric material, dissolution depends on the thickness and aqueous solubility of the polymers. In capsules the coated granules were fully dispersed in the GIT after 10-12 hrs whereas in tablets the release rate is affected by the influence of the excipients and compression.
The effective diffusion path length across a hydrogel is estimated by the thickness of hydrogel. These factors, in turn, are most influenced by the composition and crosslinking density of the hydrogel polymer network. The porosity of hydrogels arose from evaporation of water during the process of freeze drying without affecting the morphology of hydrogels .
Therefore, pH-sensitive DDSs have been extensively investigated, aiming at tumor-targeted delivery through exploiting the pH gradient existing between the normal and tumor tissues. To facilitate drug delivery and improve therapeutic effect, prodrugs, liposomes and microchips have also been designed to respond to different stimuli. Prodrugs can be tailored to contain pH-sensitive linkages for responding to a pH gradient; however, introduction of the chemical linkages to the molecular structure of drugs poses a risk of lowering binding constant of drugs to target biomolecules and thus decreasing drug efficacy . Microchips can be produced to generate the ideal responsiveness and be applied to all kinds of drugs; however, safety of microchips should be further verified in the future .
16. A controlled release pharmaceutical comprising a biologically active copolymer selected from the group consisting of poly (acrylic acid/L-dopa), poly (methacrylic acid/ L-dopa), poly (acrylic acid/carbidopa), poly (methacrylic acid/carbidopa) or combinations thereof and a pharmaceutically acceptable vehicle. 15. The controlled release pharmaceutical according to claim 12 which comprises poly (methacrylic acid/L-Î±- methyldopa) and a pharmaceutically acceptable vehicle.
As mentioned in the above cited documents representative of the state of the art, the challenge in maximizing drug effectiveness and minimizing deleterious side effects is to increase drug bioavailability and simultaneously reduce the drug amount in the medicine. According to the present invention, this is accomplished by providing a copolymer obtained by reacting L-dopa, carbidopa or L-Î±-methyldopa with a mucoadhesive polymer, such as poly (acrylic acid) or poly (methacrylic acid).
The pH sensitivity plays a major role in oral drug delivery as a result of different pH in the body segments. The hydrogels possess the characteristics of pH sensitivity . Hydrogels of poly(methacrylic acid-co-N-vinyl pyrrolidone) were synthesized and evaluated for their use as carriers for oral protein delivery. Insulin loading efficiencies were determined to be near 90% for carriers crosslinked with ethylene glycol dimethacrylate with corresponding weight incorporation levels near 12%.
Hence, percentage swelling is higher in basic pH and glipizide is easily released through large, open channel like structures. Even after 92 years of discovery, insulin faces lots of challenges in its widely accepted way of oral delivery. Oral delivery of insulin is accompanied by different advantages like rapid hepatic insulinization, prevention of peripheral hyperinsulinemia, weight gain, hypoglycemia, and higher patient compliance . However, there are disadvantages as well; being protein in nature, insulin undergoes degradation by enzymes in acidic milieu stomach and its permeability across the intestinal wall is very poor.
Int. J. Pharm.
Having pH-sensitivity, cationic polymers can mask the taste of drugs and release drugs in the stomach by responding to gastric low pH. Anionic polymers responsive to intestinal high pH are used for preventing gastric degradation of drug, colon drug delivery and achieving high bioavailability of weak basic drugs. Tumor-targeted DDSs have been developed based on polymers with imidazole groups or poly(Î²-amino ester) responsive to tumoral low pH. Polymers with pH-sensitive chemical linkages, such as hydrazone, acetal, ortho ester and vinyl ester, pH-sensitive cell-penetrating peptides and cationic polymers undergoing pH-dependent protonation have been studied to utilize the pH gradient along the endocytic pathway for intracellular drug delivery. As ion-sensitive polymers, ion-exchange resins are frequently used for taste-masking, counterion-responsive drug release and sustained drug release. Polymers responding to ions in the saliva and gastrointestinal fluids are also used for controlled drug release in oral drug formulations.