1. Introduction
Innovative approaches and advancements in biomedical science help in providing improved drug delivery systems. Formulation of advanced and productive drug delivery systems are a necessity to provide better treatment of different diseases [
1]. Oral route is the most acceptable route of drug delivery for the greatest number of patients mainly because of its low cost compared to other dosage forms. Moreover, it is a safe route with an effective outcome and also oral dosage forms are easily ingested. Conventional immediate release oral dosage forms require frequent daily dosing leading to fluctuation of drug level in plasma, which imparts a negative effect on the drug efficacy. Controlled release (CR) tablets are developed not only to surmount the demerits of older oral dosage forms but also to provide other useful advantages [
2]. CR systems maintain steady state concentration of drug in plasma and thereby reduce the frequency of daily dose. CR tablets usually face the problem of dose dumping when they undergo disintegration process, which results in severe toxicity. Such demerits are usually overcome by using diverse polymers in controlled release systems. Utilization of polymers has highly impacted the advancement of modern medicine and has led towards increased patient compliance [
3,
4]. Biocompatible polymers are widely employed in controlled release systems, which can release drug over long intervals of time. Polymeric based drug carriers display lesser side effects and also provide potential for site specific drug delivery [
5].
Polymers that display changes in their physical characteristics when external stimuli are applied are termed as stimuli-responsive polymers [
6]. Such polymers can be employed to achieve any particular targeted area drug release [
7]. They are also employed in hydrogels fabrication [
8,
9]. Hydrogels are 3D polymeric cross-linked network like structures displaying high hydrophilicity. They are also termed as smart or intelligent systems as they are engineered to be sensitive to environmental stimuli. Hydrogels are widely applicable in diverse biomedical, environmental, and pharmaceutical fields, such as tissue engineering, contact lens, immune-therapy, and most importantly in controlled drug release. Their attractive feature of displaying swelling behavior and releasing entrapped drug molecules upon change in pH and other stimuli such as temperature, light, pressure, and electric field makes them compatible for usage in controlled and targeted drug delivery systems [
10]. Free radical polymerization is a widely used method for cross-linking the hydrogels structure [
11,
12].
Hydroxypropyl methylcellulose (HPMC) is a cellulose derivative, which is water soluble in nature. It is widely employed in many industries like food, plastic, and most importantly, the pharmaceutical industry. Many grades of HPMC are used in formulation of several oral dosage forms. HPMC finds its diverse applications in oral dosages due to its biocompatibility, biodegradability, hydrophilicity, and swelling ability [
13].
Pectin is a naturally occurring polysaccharide having a complex structure with hydrophilic characteristic. Pectin is nontoxic, biocompatible, and economic in cost, which is why it has many applications in biotechnology and pharmaceuticals. It has been generally used as stabilizer and gelling agent as well as polymer in hydrogel formation [
14].
Galantamine hydrobromide (GH) is an antidementia drug, which is used in treatment of Alzheimer based dementia. Because of its short half-life of 7 h, it is administrated two times a day. Dementia is a neurodegenerative syndrome related to memory loss, mental confusion, and motor dysfunctions. The pharmacological class of Galantamine hydrobromide is cholinesterase inhibitor. It is a reversible competitive inhibitor of acetylcholine esterase. It is metabolized by cytochrome P450, 2D6, and 3A4 enzymes. Drugs that are metabolized through these enzymes affect the pharmacokinetics of Galantamine hydrobromide if they are coadministered [
15].
Hydrogels are three dimensional networks that have the ability to absorb a large amount water. These have resemblance to natural tissues because of their soft, elastic nature and low interfacial tension. These are widely employed in the pharmaceutical, agriculture, and medical sector because of their tunable properties, biocompatibility, and gel forming ability. These intelligent networks can be prepared by a number of techniques, but the most widely used approach is aqueous free radical polymerization [
16].
In this study, MBA cross-linked HPMC-pectin-co-acrylic acid hydrogels were fabricated by free radical polymerization for controlled delivery of Galantamine hydrobromide. Controlled release oral hydrogels of Galantamine hydrobromide can give a better and more efficient way of administrating the therapeutic amount of drug as a single dose, thereby reducing the frequency of dosing. Such a system shall maintain the steady state drug plasma levels, which would be beneficial for dementia patients as they are much more reluctant to take their medications and also often forget to take their medicines because of their mental condition. In this study, nine hydrogels formulations were prepared by varying the amount of polymers, monomer, and cross-linker. The fabricated hydrogels were evaluated by different characterization tests, and their in vitro drug release profile was studied.
4. Conclusions
HPMC-pectin-co-acrylic acid hydrogels were successfully fabricated through chemically cross-linked method (free radical polymerization technique). Formulated hydrogels showed pH-dependent swelling and release behavior for controlled delivery of Galantamine hydrobromide. Equilibrium swelling percentage was high, i.e., 96.87% at pH 7.4, whereas, at pH 1.2, up to 10% swelling percentage was observed. Swelling and release results depends on the amount of pectin, acrylic acid, HPMC, and MBA. As HPMC and acrylic acid amount was increased, swelling and release percentages were observed to be simultaneously increased but not in case of pectin. Higher pectin amount provided higher degree of swelling but lower level of drug release. MBA produced an inverse effect on swelling and release kinetics. The high amount of MBA leads to a lower amount of swelling and release. FTIR, DSC, TGA, and XRD confirmed the complex formation of hydrogel, which was more thermally stable as compared to individual ingredients. Gel fraction results were also directly proportional to HPMC, pectin, acrylic acid, and MBA amount. Mechanical strength of HPMC-pectin-co-acrylic acid hydrogel was excellent having capability to hold out against biological stress. EDX results confirmed loading of Galantamine hydrobromide into formulated hydrogel. In toxicity studies, blood samples and histomicrographs showed that fabricated hydrogel was safe, nontoxic, and compatible to living tissues. It was concluded that formulated hydrogels displayed pH dependent behavior and smart response to their environmental conditions. Thus, that is why they can be efficiently used in Alzheimer-related dementia where controlled delivery of Galantamine hydrobromide would be provided. Hence, dosing frequency would be reduced, which would ultimately lead to enhanced patient compliance.