Design, Optimization, and Correlation of In Vitro/In Vivo Disintegration of Novel Fast Orally Disintegrating Tablet of High Dose Metformin Hydrochloride Using Moisture Activated Dry Granulation Process and Quality by Design Approach

Alhussain H Aodah; Mohamed H Fayed; Ahmed Alalaiwe; Bader B Alsulays; Mohammed F Aldawsari; El-Sayed Khafagy

doi:10.3390/pharmaceutics12070598

Design, Optimization, and Correlation of In Vitro/In Vivo Disintegration of Novel Fast Orally Disintegrating Tablet of High Dose Metformin Hydrochloride Using Moisture Activated Dry Granulation Process and Quality by Design Approach

Pharmaceutics. 2020 Jun 27;12(7):598. doi: 10.3390/pharmaceutics12070598.

Authors

Alhussain H Aodah¹, Mohamed H Fayed^{1

2}, Ahmed Alalaiwe¹, Bader B Alsulays¹, Mohammed F Aldawsari¹, El-Sayed Khafagy^{1

3}

Affiliations

¹ Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.
² Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
³ Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.

Abstract

Compression of cohesive, poorly compactable, and high-dose metformin hydrochloride into the orally disintegrating tablet (ODT) is challenging. The objective of this study was to develop metformin ODT using the moisture activated dry granulation (MADG) process. There are no reports in the literature regarding the development of ODT based on MADG technology. The feasibility of developing metformin ODT was assessed utilizing a 3² full factorial design to elucidate the influence of water amount (X₁) and the amount of pregelatinized starch (PGS; X₂) as independent variables on key granules and tablets' characteristics. The prepared granules and tablets were characterized for granule size, bulk density, flow properties, tablets' weight variation, breaking force, friability, capping tendency, in vitro and in vivo disintegration, and drug release. Regression analysis showed that X₁ and X₂ had a significant (p ≤ 0.05) impact on key granules and tablets' properties with a predominant effect of the water amount. Otherwise, the amount of PGS had a pronounced effect on tablet disintegration. Optimized ODT was found to show better mechanical strength, low friability, and short disintegration time in the oral cavity. Finally, this technique is expected to provide better ODT for many kinds of high-dose drugs that can improve the quality of life of patients.

Keywords: high drug loading; metformin hydrochloride; moisture activated dry granulation (MADG); orally disintegrating tablet (ODT); quality-by-design (QbD).