News from Europe's pharmaceutical manufacturing industry coupled with upcoming events, and exclusive articles and interviews from industry experts. WEEKLY
Solid-State Characterization and Dissolution Properties of Lovastatin Hydroxypropyl-β-Cyclodextrin Inclusion Complex
The objectives of this study were to prepare and characterize inclusion complexes of lovastatin with hydroxypropyl-β-cyclodextrin (HPβ-CD) and to study the effect of the complexes on the dissolution rate of lovastatin (LVS). The findings suggest that LVS's poor dissolution profile can be overcome by preparing its inclusion complex with HPβ-CD.
Figure 8: In vitro dissolution profiles of pure lovastatin and its physical mixture and complexes in dissolution media-B (phosphate
buffer [pH 6.8]) (tests were done in triplicate). CPK is the kneading method, CPC is the coevaporation method, PM is the physical
mixure, and LVS is lovastatin.
The improvement in wettability of LVS by the physical mixture, the kneading method, and the coevaporation method is shown
in Figure 6. The kneading method and the coevaporation method showed highest wettability in water (99.82% and 90.04%, respectively),
as compared with plain LVS (31.88%). Even the physical mixture of HPβ-CD with LVS enhances the wettability of LVS in water
significantly. The % porosity of LVS, the physical mixture, and complexes prepared by the coevaporation and the kneading methods
were 0.54 (±0.02), 0.72 (±0.08), 0.98 (±0.06), and 1.03 (±0.07), which ruled out a possible improvement in wettability because
of variation in the samples' porosity.
Figure 9: Comparative drug-release profiles of conventional tablets containing lovastatin (LVS) and tablets containing a complex
made with the kneading method (CPK) in dissolution media-A (0.1 N HCl) and dissolution media-B (phosphate buffer [pH 6.8])
(tests performed in triplicate).
It is generally accepted that the dissolution media are not completely representative of gastrointestinal conditions, yet
it is proposed in guidelines that a good method will use a dissolution media that is physiologically meaningful or closely
mimics in vivo conditions (30, 31). It has been suggested that the inclusion of surface active agents in dissolution media is important
for poorly soluble compounds because the lack of surface tension-lowering agents would result in poorer wetting and in vitro dissolution rates that are not representative of in vivo rates (32). FDA has promoted the use of surfactants in media for conducting dissolution studies of poorly soluble compounds
(33, 34).
Dissolution studies of pure LVS and all other prepared systems (complexes and physical mixture) were carried out in dissolution
media (0.1 N HCl and phosphate buffer pH 6.8) containing aqueous sodium lauryl sulfate solution (0.25% w/v) because sodium
lauryl sulfate showed minimal surface tension at 0.2% with no significant change at higher concentrations (35, 36). When the
LVS was dispersed on the surface of the aqueous surfactant solution, LVS rapidly left the surface and was dispersed in the
bulk of solution, which indicates wetting of LVS, unlike pure water.
Rakesh P. Patel is an associate professor in the Department of Pharmaceutics and Pharmaceutical Technology, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Gujarat, India.
Articles by Rakesh P. Patel
Madhabhai M. Patel
Madhabhai M. Patel is a professor in the Department of Pharmaceutics, Kalol Pharmacy College, Kalol, Gujarat, India.
Articles by Madhabhai M. Patel
Survey
What is the single greatest threat to maintaining manufacturing processes at your facility?
