Temperature- and pH-Dependent Drug Release of Block Copolymers of Methacrylic Acid and Poly

It does granulation of drug substances for controlled release, effective and stable enteric coatings with a fast dissolution in the upper bowel. It shows variable release profiles with site specific drug delivery in intestine in combination with Eudragit ® S grades [33 Raymond CR, Paul JS, Marian EQ. Handbook of pharmaceutical excipients, Pharmaceutical Press and American Pharmacists Association. The drug administered orally encounters various spectrums of pH ranges in the GIT. As most of the drugs are weak acid or weak basis so their release from formulations are pH dependent thus could be controlled by adding buffers to the formulation. When gastric fluid enters the membrane, the buffer adjusts the polymer pH inside and imparts constant drug release.

There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network.

These hydrogels were immersed in buffer solutions of pH 7.4 and pH 1.2. The swelling results demonstrated that swelling of hydrogel depended on the pH of swelling medium, amount of N-succinyl chitosan and Poly (AAm-co-AA), and crosslinking agent concentration [60]. The results of swelling ratio at pH 7.4 and pH 1.2 are shown in Fig 7. It can be seen that hydrogels showed higher swelling at pH 7.4 and lower swelling ratio at pH 1.2. The higher swelling at pH 7.4 might be due to presence of greater number of carboxylic groups.

Poly(acrylamide-co-acrylic acid)-spirulina (AAm-AAc-Sp) hydrogels were prepared by free radical solution polymerization of the monomer acrylamide (AAm) and the comonomer acrylic acid (AAc) with N,N-methylene bisacrylamide (BAAm) as the crosslinker in the presence of spirulina (Sp), which is a microalga species. The swelling ratios of the hydrogels were followed by gravimetric measurements. Hence, swelling kinetics and diffusion parameters were determined. Furthermore, the morphological structures and mechanical behaviors of the hydrogels were investigated by scanning electron microscopy and by using a uniaxial compression machine, respectively. All the results showed that spirulina had strong influence in the pH-dependent swelling behavior, as well as on the kinetic and diffusion parameters due to its interaction with the acrylic acid units.

In the same study, the PEG-doxorubicin conjugates showed longer plasma half-life and approximately 2 times higher tumor accumulation in mice than did free drug after intravenous administration. In this study, about 30% of drug was rapidly cleared from the bloodstream, implying the ability of the conjugates to escape from the RES might be insufficient. Stimuli-responsive polymers are one of the most important excipients in DDSs and pharmaceutical formulations for site-specific drug release as they can be designed to produce specific and desired pH- or ionic concentration-triggered response according to the variations in physiological environments in the human body.

The anionic nature of alginate, its derivatives, its blends, and its polyelectrolyte complexes makes it a suitable carrier for pH sensitive drug release for different drugs. Jao et al. loaded ampicillin in calcium alginate hydrogels and studied the mechanism of controlled release of the drug in simulated physiological fluids. The study of drug release in SIF (pH 7.4) and SGF (pH 1.2) showed that the drug release is pH dependent and negligible release in SGF while maximum release in SIF was observed [94]. Chen et al. blended alginate with N ,O -carboxymethyl chitosan (NOCC) cross-linked with genipin and studied pH dependent release behavior of the loaded model protein drug, BSA.

This leads to a transition from a random coil conformation to an amphipathic α-helical conformation, allowing the peptide to interact with and destroy the endo/lysosomal membrane and eventually escape to the cytoplasm [76]. Hemagglutinin is one of major glycoproteins on influenza virus. Under the acidic pH inside the endosomes, conformational change of the hemagglutinin from random coil to α-helix allows the protein to be inserted into the endosomal membrane, resulting in fusion between the virus envelope and the endosomal membrane and the release of the nucleocapsid of the virus into the cytoplasm of the infected cell [77]. N-terminus of the hemagglutinin HA2(1-23) (GLFGAIAGFIENGWEGMIDGWYG) is a pH-sensitive cell-penetrating peptide useful for endosomal escape.

The results showed that the prepared hydrogels are a successful synthesis for pH dependent delivery of drugs [150]. Chronic conditions of general anxiety disorder (GAD), epilepsy. and neuropathic pain are managed by introducing the sustained release of second generation anticonvulsant drugs like pregabalin (PGB). Cevik et al. introduced a novel method of visible light induced synthesis of pH sensitive hydrogels for delivery of pregabalin at intestinal pH. The hydrophobic styrene-butadiene-styrene (SBS) copolymer was incorporated into the pH responsive methacrylic acid-g -ethylene glycol P(MAA-g -EG) prepolymer for increased integrity and hydrophobic function. The prepared P(MAA-g -EG) hydrogels showed high swelling at high pH 7.4 and nearly 86% drug release whereas low swelling and less drug release (15.3%) at low pH. With SBS incorporated into the pH sensitive prepolymer, swelling decreased and drug release was 79.5% at pH 7.4 and only 14.9% at pH 1.2 [130].

2.1 Polymers responsive to stomach low pH

The embedding of this polymer resulted in apparently reduction in pore size [59]. However, the pore size is more uniform as compared to SP1 which shows the proper embedding of the Poly (AAm-co-AA).

V. Degradation in human intestinal incubation models. Eur.

They observed that these covalently cross-linked hydrogels were pH sensitive and showed maximum swelling and drug release at low pH in the stomach environment owing to protonation of an amino group achieving the targeted sustained release. The purpose of introducing acrylic acid as graft is to control the swelling (to avoid burst release) and to achieve sustained release of the antibiotic [125]. Poly(vinyl pyrrolidone) (PVP) is highly water soluble with excellent properties like biocompatibility and absorbancy but poor mechanical properties. However, to overcome the poor mechanical properties, PVP can be grafted, or its monomer, N -vinyl pyrrolidone, can be copolymerized with some other vinylic monomers such as acrylic acid, methacrylic acid, methacrylamide, etc.

poly methacrylate stomach acid

Initially, 11.5% moisture weight loss can be observed in the range of 40-90°C. Modified chitosan showed 18% weight loss in the range of 200-300°C and this loss is due to degradation of polysaccharide backbone. A new stage of weight loss was observed in the range of 300-430°C due to degradation of succinyl group. At this stage, 30% loss in weight was observed [55]. This third stage of weight loss confirmed the successful succinylation of chitosan, and formation of NSC.

poly methacrylate stomach acid

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