Pharmaceutical Research

, Volume 29, Issue 10, pp 2660–2683

Impact of Excipient Interactions on Solid Dosage Form Stability

Expert Review

DOI: 10.1007/s11095-012-0782-9

Cite this article as:
Narang, A.S., Desai, D. & Badawy, S. Pharm Res (2012) 29: 2660. doi:10.1007/s11095-012-0782-9

ABSTRACT

Drug-excipient interactions in solid dosage forms can affect drug product stability in physical aspects such as organoleptic changes and dissolution slowdown, or chemically by causing drug degradation. Recent research has allowed the distinction in chemical instability resulting from direct drug-excipient interactions and from drug interactions with excipient impurities. A review of chemical instability in solid dosage forms highlights common mechanistic themes applicable to multiple degradation pathways. These common themes include the role of water and microenvironmental pH. In addition, special aspects of solid-state reactions with excipients and/or excipient impurities add to the complexity in understanding and modeling reaction pathways. This paper discusses mechanistic basis of known drug-excipient interactions with case studies and provides an overview of common underlying themes. Recent developments in the understanding of degradation pathways further impact methodologies used in the pharmaceutical industry for prospective stability assessment. This paper discusses these emerging aspects in terms of limitations of drug-excipient compatibility studies, emerging paradigms in accelerated stability testing, and application of mathematical modeling for prediction of drug product stability.

KEY WORDS

capsulescompatibilitydegradationdissolutionexcipientsgranulesimpuritiesmechanismreactionstabilitytablets

Abbreviations

Alu

aluminum

API

active pharmaceutical ingredient

ARP

Amadori rearrangement product

BHA

butylated hydroxyanisole

BHT

butylated hydroxytoluene

GC

gas chromatography

HCl

hydrochloride

HCTZ

hydrochlorothiazide

HDPE

high density polyethylene

HPLC

high performance liquid chromatography

HPMC

hydroxypropyl methylcellulose

HPO

hydroperoxide

ICH

international conference on harmonization

LC/MS

liquid chromatography tandem with mass spectroscopy

MVTR

moisture vapor transmission rate

NF

National Formulary

NMR

nuclear magnetic resonance (spectroscopy)

PEG

polyethylene glycol

pHmax

pH of maximum solubility

PVA

polyvinyl alcohol

PVP

polyvinyl pyrrolidone (povidone)

PhEur

European Pharmacopeia

PVP-VA

polyvinylpyrrolidone-vinyl acetate copolymer

PXRD

powder X-ray diffraction

SDMT

sorption desorption moisture transfer

ssNMR

solid state NMR

USP

United States Pharmacopeia

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Ajit S. Narang
    • 1
  • Divyakant Desai
    • 1
  • Sherif Badawy
    • 1
  1. 1.Drug Product Science and TechnologyBristol-Myers Squibb, Co.New BrunswickUSA