The influence of excipients on physical and pharmaceutical properties of oral lyophilisates containing a pregabalin-acetaminophen combination

ABSTRACT

Objectives: The purpose of the study was to investigate and characterize the oral lyophilisates containing the pregabalin-acetaminophen drug combination and as xcipients mannitol with microcrystalline cellulose or hydroxypropyl methylcellulose, in order to conclude upon drug-excipient interactions and their stability implications, impact of excipients on drug release and on the physicochemical and mechanical properties of the pharmaceutical formulations.

Methods: The oral tablets were made by using a Christ freeze-dryer alpha 2–4-LSC lyophilizer, and evaluated for stability, drug-excipient compatibility and homogeneity of the prepared pharmaceutical formulations. The formulations were evaluated for in vivo absorption in rabbits by histopathological exams.

Results: FTIR and thermogravimetric analyses, DLS technique, SEM and NIR-CI studies confirmed the compatibility between compounds. From the determined physical and biochemical parameters of the formulations it was established that they are stable, homogeneous, and meet the conditions for orally disintegrating tablets.

Conclusion: In the case of the investigated pharmaceutical formulations the study evidenced the assembling through physical bonds between the excipients and the ‘codrug’ complex, which do not affect the release of the bioactive compounds.

KEYWORDS:

• Pregabalin-acetaminophen combination
• mannitol
• microcrystalline cellulose
• hydroxypropyl methylcellulose
• thermal analysis
• near infrared chemical imaging

Acknowledgments

The authors wish to thank and appreciate their colleague Dr. Daniel Timpu from the ‘P.Poni’ Institute of Macromolecular Chemistry for his expert assistance in Wide angle X-ray diffraction analyses.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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Funding

‘Petru Poni’ Institute of Macromolecular Chemistry, Grigore Ghica Voda Alley 41 A, RO–700487 Iasi, Romania, and Department of Pharmaceutical Technology and Department of Pharmacology-Algesiology, Faculty of Pharmacy, University of Medicine and Pharmacy ‘Grigore T. Popa’ University Street 16, 700115 Iasi, Romania