Solid-State Characterization and Dissolution Properties of Lovastatin Hydroxypropyl-β-Cyclodextrin Inclusion Complex - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

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.


Pharmaceutical Technology


Linearity was characteristic of the AL-type system (19) and suggested that water-soluble complexes formed in the solution. Furthermore, the slope value (0.0011) was lower than 1.0, thus indicating that inclusion complexes in a molar ratio of 1:1 formed between the guest (LVS) and host (HPβ-CD) molecules. The stability constant (Kc) for the complexes at 37 C (assuming a 1:1 stoichiometry) calculated from the slope of the initial straight portion of the solubility diagram was 917.67 M–1 , which indicated a suitable and stable complex formation. It is reported that cyclodextrin-drug complexes with Kc values in the range of 200–5000 M–1 show improved dissolution properties and, hence, better bioavailabilities (19).

The values of Gibbs free energy change (ΔGtr) were calculated to understand transfer process of LVS from pure water to aqueous solution of HPβ-CD. The ΔGtr values of LVS from pure water to aqueous solutions with various concentrations of HPβ-CD at 37 C were calculated using the following equation (25):











in which So/Ss is the ratio of molar solubility of LVS in an aqueous solution of HPβ-CD to that of the pure water. The obtained values of Gibbs free energy are shown in Table II. The ΔGtr values provide information about whether the reaction condition is favorable or unfavorable for drug solubilization in the aqueous carrier solution. Negative Gibbs free energy values indicate favorable conditions. The ΔGtr values were all negative for HPβ-CD at various concentrations, thus indicating the spontaneous nature of LVS solubilization. These values decreased with increased concentration of HPβ-CD, thereby demonstrating that the reaction became more favorable as the concentration of HPβ-CD increased.

Drug content. The drug content (%w/w) of the complexes prepared by the coevaporation and the kneading methods and the physical mixture were found to be 21.02 (0.23)%, 20.78 (0.39)%, and 14.74 (5.35)%, respectively, which corresponds approximately with the stoichiometric ratio of the complex and indicates chemical stability and content uniformity of LVS in its complex form. The content uniformity for the physical mixture is lower than the complexes prepared by the coevaporation and the kneading methods. This effect may be attributed to insufficient mixing caused by simple mixing of powders without applying pressure (HPβ-CD and LVS). The final moisture content of the pure drug, the physical mixture, and the complex prepared by the coevaporation and the kneading methods were 0.23%, 0.89%, 1.09%, and 1.14%, respectively.

Characterization of complexes. IR spectroscopic analysis. Fourier transform infrared spectroscopy (FT IR) has been used to assess the interaction between β-CD and guest molecules in the solid state. Upon complexion, the peak band of the guest shifts in the absorption spectrum. Nonetheless, some of the changes are very subtle and require careful interpretation of the spectrum (26).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
70%
Breakthrough designations
4%
Protecting the supply chain
17%
Expedited reviews of drug submissions
2%
More stakeholder involvement
7%
View Results
Eric Langerr Outsourcing Outlook Eric LangerTargeting Different Off-Shore Destinations
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerAsymmetric Synthesis Continues to Advance
Jill Wechsler Regulatory Watch Jill Wechsler Data Integrity Key to GMP Compliance
Sean Milmo European Regulatory WatchSean MilmoExtending the Scope of Pharmacovigilance Comes at a Price
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Ebola Outbreak Raises Ethical Issues
Better Comms Means a Fitter Future for Pharma, Part 2: Realizing the Benefits of Unified Communications
Better Comms Means a Fitter Future for Pharma, Part 1: Challenges and Changes
Source: Pharmaceutical Technology,
Click here