Muhammad Adnan Zia1, Muhammad Sohail1, Muhammad Usman Minhas2, Rai Muhammad Sarfraz2, Shahzeb Khan3,4,5, Marcel de Matas6, Zahid Hussain7, Mudassir Abbasi1, Syed Ahmed Shah1, Mubeen Kousar1, Naveed Ahmad8. 1. Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Pakistan. 2. College of Pharmacy, University of Sargodha, Sargodha, Pakistan. 3. Department of Pharmacy, University of Malakand, KPK, Pakistan. 4. Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA. 5. Discipline of Pharmaceutical Sciences, School of Health Sciences, UKZN, Durban, South Africa. 6. SEDA Pharmaceutical Development Services, Cheshire, UK. 7. Department of Pharmaceutics & Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah, UAE. 8. Institute of Pharmaceutical Sciences, Kings College London UK, London, UK.
Abstract
Objectives: The study aimed to develop safe, effective, and targeted drug delivery system for administration of nonsteroidal anti-inflammatory drugs (NSAIDs) in the form of microgels. We developed pH responsive microgels to overcome the mucosal damage caused by traditional immediate release dosage forms. Colon targeting and controlled release formulations have the potential to improve efficacy and reduce undesirable effects associated with NSAIDs. Methods: The pH sensitive oral hydrogel demonstrates the potential to target the colon. Cellulose acetate phthalate (CAP) and hydroxyethyl methacrylate (HEMA) based microgel particles were produced using a free radical polymerization technique using ammonium persulfate (APS) initiator and methylenebisacrylamide (MBA) as the crosslinking agent. Swelling and in-vitro drug release studies were performed at a range of pH conditions. The produced formulations were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy (SEM), and X-ray diffraction. Biocompatibility of the microgels was analyzed in cytotoxicity studies.Key findings: The swelling and release rate were negligible at pH 1.2, which confirmed the pH-responsiveness of CAP-co-poly(HEMA). The co-polymeric system prevents the release of ketoprofen sodium in the stomach owing to limited swelling at gastric pH, whilst promoting release at the basic pH observed in the colon. SEM images confirmed porous nature of the microgels that facilitate effective drug diffusion through the polymeric matrix. Cytotoxicity studies revealed biocompatibility of hydrogels. Conclusion: These investigations showed that that the controlled drug release and gastro-protective drug delivery of NSAIDS was achieved using CAP-co-poly(HEMA) microgel particles.
Objectives: The study aimed to develop safe, effective, and targeted drug delivery system for administration of nonsteroidal anti-inflammatory drugs (NSAIDs) in the form of microgels. We developed pH responsive microgels to overcome the mucosal damage caused by traditional immediate release dosage forms. Colon targeting and controlled release formulations have the potential to improve efficacy and reduce undesirable effects associated with NSAIDs. Methods: The pH sensitive oral hydrogel demonstrates the potential to target the colon. Cellulose acetate phthalate (CAP) and hydroxyethyl methacrylate (HEMA) based microgel particles were produced using a free radical polymerization technique using ammonium persulfate (APS) initiator and methylenebisacrylamide (MBA) as the crosslinking agent. Swelling and in-vitro drug release studies were performed at a range of pH conditions. The produced formulations were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy (SEM), and X-ray diffraction. Biocompatibility of the microgels was analyzed in cytotoxicity studies.Key findings: The swelling and release rate were negligible at pH 1.2, which confirmed the pH-responsiveness of CAP-co-poly(HEMA). The co-polymeric system prevents the release of ketoprofen sodium in the stomach owing to limited swelling at gastric pH, whilst promoting release at the basic pH observed in the colon. SEM images confirmed porous nature of the microgels that facilitate effective drug diffusion through the polymeric matrix. Cytotoxicity studies revealed biocompatibility of hydrogels. Conclusion: These investigations showed that that the controlled drug release and gastro-protective drug delivery of NSAIDS was achieved using CAP-co-poly(HEMA) microgel particles.
Authors: Mohammad F Bayan; Saeed M Marji; Mutaz S Salem; M Yasmin Begum; Kumarappan Chidambaram; Balakumar Chandrasekaran Journal: Polymers (Basel) Date: 2022-09-05 Impact factor: 4.967