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

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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


Coevaporation method. Methanol and water were used as solvents to prepare the complex by a coevaporation method. The required quantities of LVS and HPβ-CD were dissolved in methanol and water, respectively. Both the solutions were mixed and solvents were evaporated by controlled heating at 45–50 C. The resultant solid was pulverized and then put through a 120 # sieve.

Kneading method. The required quantities of HPβ-CD and distilled water were mixed together in a motor to obtain a homogeneous paste. Then, LVS was added slowly; while grinding, a small quantity of methanol was added to assist the dissolution of LVS. The mixture was then ground for 1 h. During this process, an appropriate quantity of water was added to the mixture to maintain a suitable consistency. The paste was dried in an oven at 45–50 C for 24 h. The dried complex was pulverized and then put through a 120 # sieve.

Drug content. The complexes prepared by kneading, coevaporation, and physical mixture were assayed for LVS content by dissolving a specific amount of the complex in methanol and analyzing for the LVS content spectrophotometrically at 238.2 nm on spectrophotometer (ultraviolet-vis spectrophotometer, Shimazdu-1601). The final moisture contents of all samples were measured with an electronic moisture balance (Sartorius, model MA-45, Goettingen, Germany).

Characterization of complexes. Infrared (IR) spectroscopic analysis. The IR spectra of moisture-free powdered samples of LVS, HPβ-CD, the physical mixture , and the complex prepared by the coevaporation and the kneading methods were obtained using a spectrometer (FTIR-8300, Shimadzu Co., Kyoto, Japan) with a potassium bromide (KBr) pellet method.

Powder X-ray diffraction (PXRD) analysis. PXRD patterns of LVS, HPβ-CD, the physical mixture, and complexes prepared by the coevaporation and the kneading methods were determined using a scanner (Phillips PW 3710) and a generator (IW 1830) with a CuK α anode at 40 kV and 30 mA at a scan rate of 1 min–1 from 2θ range from 1 to 40.

Differential scanning calorimetry (DSC) analysis. DSC scans of the powdered sample of LVS, β-CD, the physical mixture, and complexes prepared by the coevaporation and the kneading methods were recorded using a DSC instrument (Shimadzu 60) with TDA trend-line software. The samples (6–7 mg) were weighed accurately in crimped aluminum pans and heated from 50 C to 300 C at a scanning rate of 10 C /min under dry nitrogen flow (100 mL/min).

Wettability and dissolution studies. The wettability study was performed using open tubes containing LVS, the physical mixture, and complexes prepared by the coevaporation and the kneading methods. The tubes were placed with their lower capillary ends dipped into colored water (0.01% eosin in water). The upward migration of the colored front was registered as a function of time. The porosity of all samples also was measured using a mercury porosimeter (PoreMaster 60, Quantachrome Instruments, Boynton Beach, FL). Porosity is defined as the percentage of void space in a solid. Mercury density (ρHg) and helium density (PHe) values often are used to evaluate % porosity (€) (20). Each test was repeated four times and the mean was calculated.


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