Comparative Evaluation for Controlled Release of Amoxicillin from RSM-CCD-Optimized Nanocomposites Based on Sodium Alginate and Chitosan-Containing Inclusion Complexes

• Published in: Molecular pharmaceutics Vol. 18; no. 10; pp. 3795 - 3810
• Main Authors: Khushbu, Jindal, Rajeev
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 04.10.2021
• Subjects: Alginates; Amoxicillin - administration & dosage; Amoxicillin - pharmacokinetics; Chitosan; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - pharmacokinetics; Humans; Kinetics; Nanocomposites - administration & dosage; Nanoparticle Drug Delivery System - administration & dosage; Nanoparticle Drug Delivery System - pharmacokinetics; amoxicillin; graphene oxide; β-cyclodextrin; nanocomposites
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.1c00340

Amoxicillin (AMX) is a semisynthetic antibiotic, an analogue of ampicillin, with a wide spectrum of bacterial activity against many microorganisms but possesses some limits. To increase the drug effectiveness, supramolecule nanocomposites composed of β-cyclodextrin (β-CD) and chitosan/sodium alginate/GO were chosen in the present study as a sustained release formulation. Nanocomposites of chitosan (CH), sodium alginate (ALG), and graphene oxide (GO) were synthesized at 50 °C. The inclusion complexes (ICs) were processed via the physical mixture (PM), kneading (KM), microwave (MW) method, or coprecipitation (CP) and directly loaded into the nanocomposite. To confirm the formation of true ICs, the ICs were analyzed by DSC, SEM, 1H NMR, 2D NMR ROESY, and XRD. A drug release study was performed to find out which method is best for the controlled release of drugs in different environments of pH 2, 7, and 7.4 at 37 °C. From the observed drug release data, it was found that PM and KM showed a burst release of drugs and the microwave method was the most suitable method to prepare exact ICs of AMX and β-CD for sustained release of drugs. Kinetics of drug release was analyzed by various kinetic models, and it was observed that the Korsmeyer–Peppas and Peppas–Sahlin models were best fit for drug release in all cases. A Phase solubility study was carried out to find the stoichiometry of IC formation and the complexation constant. The drug release was controlled and pH-dependent, confirming that nanocomposites are pH-sensitive. From drug release analysis, it was acknowledged that β-CD is capable of causing sustained drug release.