Hajra Afeera Hameed1, Shahzeb Khan1,2,3, Muhammad Shahid4, Riaz Ullah5, Ahmed Bari6, Syed Saeed Ali6, Zahid Hussain7, Muhammad Sohail8, Shafi Ullah Khan9, Thet Thet Htar9. 1. Department of Pharmacy, University of Malakand, Chakdara, Khyber Pakhtunkhwa 18800, Pakistan. 2. Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa. 3. Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA. 4. Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan. 5. Medicinal, Aromatic & Poisonous Plants Research Center (MAPPRC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. 6. Central Laboratory, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. 7. Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates. 8. Department of Pharmacy, COMSATS University Islamabad, Abbottabad 22060, Pakistan. 9. School of Pharmacy, Monash University Malaysia, Bandar Sunway, Subang Jaya 47500, Malaysia.
Abstract
BACKGROUND: Naproxen (NP) is a non-steroidal anti-inflammatory drug with poor aqueous solubility and low oral bioavailability, which may lead to therapeutic failure. NP causes crucial GIT irritation, bleeding, and peptic and duodenal ulcers. PURPOSE OF THE STUDY: This study aimed to engineer and characterize polymer hybrid enteric microspheres using an integrated (experimental and molecular modelling) approach with further development to solid dosage form with modified drug release kinetics and improved bioavailability. MATERIALS AND METHODS: NP loaded polymer hybrid enteric microspheres (PHE-Ms) were fabricated by using a modified solvent evaporation technique coupled with molecular modelling (MM) approach. The PHE-Ms were characterized by particle size, distribution, morphology, crystallinity, EE, drug-polymer compatibility, and DSC. The optimized NP loaded PHE-Ms were further subjected to downstream procedures including tablet dosage form development, stability studies and comparative in vitro-in vivo evaluation. RESULTS: The hydrophobic polymer EUD-L100 and hydrophilic polymer HPMC-E5 delayed and modified drug release at intestinal pH while imparting retardation of NP release at gastric pH to diminish the gastric side effects. The crystallinity of the NP loaded PHE-Ms was established through DSC and P (XRD). The particle size for the developed formulations of PEH-Ms (M1-M5) was in the range from 29.06 ±7.3-74.31 ± 17.7 μm with Span index values of 0.491-0.69, respectively. The produced NP hybrid microspheres demonstrated retarded drug release at pH 1.2 and improved dissolution at pH 6.8. The in vitro drug release patterns were fitted to various release kinetic models and the best-followed model was the Higuchi model with a release exponent "n" value > 0.5. Stability studies at different storage conditions confirmed stability of the NP loaded PHE-Ms based tablets (P<0.05). The molecular modelling (MM) study resulted in adequate binding energy of co-polymer complex SLS-Eudragit-HPMC-Naproxen (-3.9 kcal/mol). In contrast to the NP (unprocessed) and marketed formulations, a significant increase in the Cmax of PHE-MT1 (44.41±4.43) was observed. CONCLUSION: The current study concludes that developing NP loaded PHE-Ms based tablets could effectively reduce GIT consequences with restored therapeutic effects. The modified release pattern could improve the dissolution rate and enhancement of oral bioavailability. The MM study strengthens the polymer-drug relationship in microspheres.
BACKGROUND: Naproxen (NP) is a non-steroidal anti-inflammatory drug with poor aqueous solubility and low oral bioavailability, which may lead to therapeutic failure. NP causes crucial GIT irritation, bleeding, and peptic and duodenal ulcers. PURPOSE OF THE STUDY: This study aimed to engineer and characterize polymer hybrid enteric microspheres using an integrated (experimental and molecular modelling) approach with further development to solid dosage form with modified drug release kinetics and improved bioavailability. MATERIALS AND METHODS: NP loaded polymer hybrid enteric microspheres (PHE-Ms) were fabricated by using a modified solvent evaporation technique coupled with molecular modelling (MM) approach. The PHE-Ms were characterized by particle size, distribution, morphology, crystallinity, EE, drug-polymer compatibility, and DSC. The optimized NP loaded PHE-Ms were further subjected to downstream procedures including tablet dosage form development, stability studies and comparative in vitro-in vivo evaluation. RESULTS: The hydrophobic polymer EUD-L100 and hydrophilic polymer HPMC-E5 delayed and modified drug release at intestinal pH while imparting retardation of NP release at gastric pH to diminish the gastric side effects. The crystallinity of the NP loaded PHE-Ms was established through DSC and P (XRD). The particle size for the developed formulations of PEH-Ms (M1-M5) was in the range from 29.06 ±7.3-74.31 ± 17.7 μm with Span index values of 0.491-0.69, respectively. The produced NP hybrid microspheres demonstrated retarded drug release at pH 1.2 and improved dissolution at pH 6.8. The in vitro drug release patterns were fitted to various release kinetic models and the best-followed model was the Higuchi model with a release exponent "n" value > 0.5. Stability studies at different storage conditions confirmed stability of the NP loaded PHE-Ms based tablets (P<0.05). The molecular modelling (MM) study resulted in adequate binding energy of co-polymer complex SLS-Eudragit-HPMC-Naproxen (-3.9 kcal/mol). In contrast to the NP (unprocessed) and marketed formulations, a significant increase in the Cmax of PHE-MT1 (44.41±4.43) was observed. CONCLUSION: The current study concludes that developing NP loaded PHE-Ms based tablets could effectively reduce GIT consequences with restored therapeutic effects. The modified release pattern could improve the dissolution rate and enhancement of oral bioavailability. The MM study strengthens the polymer-drug relationship in microspheres.
Authors: N Venkata Naga Jyothi; P Muthu Prasanna; Suhas Narayan Sakarkar; K Surya Prabha; P Seetha Ramaiah; G Y Srawan Journal: J Microencapsul Date: 2010-05 Impact factor: 3.142
Authors: Han Bi Ji; Jae Young Hong; Cho Rim Kim; Chang Hee Min; Jae Hoon Han; Min Ji Kim; Se-Na Kim; Cheol Lee; Young Bin Choy Journal: Drug Deliv Date: 2022-12 Impact factor: 6.419