Modular solid dosage form design - Application to pH-independent release of a weak-base API

Mario A Cano-Vega; Meng Deng; Rodolfo Pinal

doi:10.1016/j.ijpharm.2021.120518

Modular solid dosage form design - Application to pH-independent release of a weak-base API

Int J Pharm. 2021 May 15:601:120518. doi: 10.1016/j.ijpharm.2021.120518. Epub 2021 Mar 26.

Authors

Mario A Cano-Vega¹, Meng Deng², Rodolfo Pinal³

Affiliations

¹ Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.
² Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA; School of Materials Engineering, Purdue University, West Lafayette, IN, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
³ Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA. Electronic address: rpinal@purdue.edu.

PMID: 33775729
DOI: 10.1016/j.ijpharm.2021.120518

Abstract

A novel approach to solid dosage form design is investigated, whereby instead of blending the ingredients and subsequently compacting the mixture, the dosage form is made by assembling prefabricated components, each with a specific function. The approach was used to formulate a weak-base API (active pharmaceutical ingredient), such that the modular dosage forms exhibited pH-independent drug release. Tablet-like dosage forms of ciprofloxacin (CPR), used as model weak-base drug, were prepared in order to generate dosage forms exhibiting pH-independent drug release. The dosage forms were made by assembling two types of prefabricated modules onto 3D stacks. The modules were hydroxypropyl methylcellulose circular film wafers, loaded with either CPR or citric acid (CA). CA-wafers served the function of pH-modifier modules in the microenvironment of the dosage form during the dissolution process. In vitro drug release from dosage forms consisting of CA- and CPR-wafers stacked in alternate sequence was compared with the release from assemblies containing CPR-wafers only, under pH = 1.2 and pH = 6.8 conditions. In the absence of CA-wafers, CPR release was ~25-fold slower at pH = 6.8 compared to pH = 1.2. Inclusion of CA-wafers in the dosage form assembly accelerated and decelerated drug release at pH = 6.8 and pH = 1.2, respectively, which resulted in overlapping drug release profiles under the two pH conditions. The two drug release profiles met the criteria for sameness as assessed by the f₁ (difference) and f₂ (similarity) factors. Modeling of drug release kinetics pointed toward polymer erosion as the primary mechanism of drug release for the overlapping pH = 1.2 and pH = 6.8 profiles. In terms of their drug release properties, the multi-modular dosage form assemblies exhibited the attributes and behavior of single bodies, rather than the combined contributions from multiple individually-operating modules. The initial geometry of the dosage form, characterized by the surface area (SA), volume (V) and SA/V ratio accounted for drug release kinetics in the same fashion as for traditional tablet compacts.

Keywords: 3D assembly; Dissolution; Excipient functionality; Modular dosage forms; Polymer films; Weak bases.

MeSH terms

Delayed-Action Preparations
Dosage Forms
Hydrogen-Ion Concentration
Hypromellose Derivatives
Solubility*
Tablets

Substances

Delayed-Action Preparations
Dosage Forms
Tablets
Hypromellose Derivatives