Formulation, Statistical Optimization, and In Vivo Pharmacodynamics of Cydonia oblonga Mucilage/Alginate Mucoadhesive Microspheres for the Delivery of Metformin HCl

Sobia Noreen; Sara Hasan; Shazia Akram Ghumman; Shoaib Anwar; Humaira Yasmeen Gondal; Fozia Batool; Shazia Noureen

doi:10.1021/acsomega.2c07789

Formulation, Statistical Optimization, and In Vivo Pharmacodynamics of Cydonia oblonga Mucilage/Alginate Mucoadhesive Microspheres for the Delivery of Metformin HCl

ACS Omega. 2023 Feb 5;8(6):5925-5938. doi: 10.1021/acsomega.2c07789. eCollection 2023 Feb 14.

Authors

Sobia Noreen¹, Sara Hasan^{1

2}, Shazia Akram Ghumman³, Shoaib Anwar¹, Humaira Yasmeen Gondal¹, Fozia Batool¹, Shazia Noureen¹

Affiliations

¹ Institute of Chemistry, University of Sargodha, Sargodha40100, Pakistan.
² Department of Chemistry, The University of Lahore, Sargodha Campus, Sargodha40100, Pakistan.
³ College of Pharmacy, University of Sargodha, Sargodha40100, Pakistan.

Abstract

In recent years, attention has shifted toward the utilization of natural polymers for encapsulation and sustained release of health-hazardous drugs. The purpose of this work is to define and assess the sustained delivery potential and mucoadhesive potential of a Cydonia oblonga mucilage (COM) and sodium alginate (Na-Alg)-constituting polymeric delivery carrier of antidiabetic drugs with a specific end goal to retain metformin HCl in the stomach while expanding the drug's bioavailability. Metformin HCl was encapsulated in mucoadhesive microspheres by an ionic gelation method. Polymers with different combinations were tried, and the resulting mucoadhesive COM/Na-Alg microspheres were assessed for particle size (mm) PS/Y₁, drug encapsulation efficiency DEE (%)/Y₂, and in vitro percentage cumulative drug release R_12h/Y₃ using Drug Design Expert software version 10. The response surface methodology by a 3²-central composite design predicted optimal synthesis parameters for the microspheres to be 295 mg for COM and 219 mg for Na-Alg. An optimized formulation was prepared under these conditions and used to evaluate the micrometric properties, morphology and structural characteristics, swelling behavior, in vitro drug release, and kinetics. Acute toxicity studies were carried out on blank COM/Na-Alg microspheres to deem them safe for in vivo studies. The DEE (%) was calculated to be 85.8 ± 1.67, whereas scanning electron microscopy (SEM) showed a coarse surface with characteristic wrinkles and cracks with an optical microscopic particle size of 0.96 ± 2.45. The ex vivo tests showed great mucoadhesive properties and good swelling behavior with pH-responsive drug release and a significant reduction in in vivo blood glucose levels. The results advocated the use of optimized microspheres to enhance the bioactivity with a possible dose reduction, making it less symptomatic, reducing the expense of the treatment, and subsequently facilitating better patient compliance.