Formulation and Evaluation of Lumefantrine Solid Dispersions for Dissolution Enhancement
A.V.S. Himabindu1*, U. Vimala Kumari2, K. Kavya2, T. Mounika2, K. Lakshmi Prasanna2,
D. Deepthi Akshaya2, K. Padmalatha2
1Associate Professor, Department of Pharmaceutics, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada – 521108.
2Department of Pharmaceutics, Vijaya Institute of Pharmaceutical Sciences for Women,
Enikepadu, Vijayawada – 521108.
*Corresponding Author E-mail: satyahimabindu@gmail.com
ABSTRACT:
Lumefantrine (LUM) is a poorly water-soluble antimalarial drug that has limited bioavailability due to its low solubility and dissolution rate. The purpose of this study was to enhance the bioavailability of lumefantrine by preparing solid dispersions using polyvinylpyrrolidone K30 (PVP K30) as a hydrophilic carrier through the fusion method and solvent evaporation method. Solid dispersions (SDs) of LUM were prepared with varying drug-to-carrier ratios (1:1, 1:2, and 1:3) to optimize the formulation for enhanced dissolution properties. The solid dispersions were evaluated for their physicochemical properties, including morphology, drug content, solubility, in vitro dissolution and stability. Fourier-transform infrared (FTIR) spectroscopy also employed to analyze the possible interaction between LUM and PVP K30. The solubility and dissolution rate of lumefantrine were significantly enhanced in the solid dispersions compared to the pure drug. The formulation prepared by the solvent evaporation method showed the highest dissolution rate and solubility. The results demonstrate that the fusion method and solvent evaporation method are effective strategies for improving the solubility and bioavailability of lumefantrine, offering a promising approach for enhancing the therapeutic efficacy of this antimalarial drug.
KEYWORDS: Lumefantrine, Solid Dispersions, Polyvinylpyrrolidone K30, Fusion Method, Solvent Evaporation Method, Bioavailability, Dissolution Rate, Antimalarial, Drug Delivery.
INTRODUCTION:
Lumefantrine (LUM) is a highly lipophilic antimalarial drug used primarily in combination with artemether for the treatment of malaria. Despite its therapeutic effectiveness, its clinical use is limited due to poor aqueous solubility, leading to low bioavailability. This poor bioavailability is often a result of the drug's low solubility in the gastrointestinal tract, which in turn impairs its absorption and limits its therapeutic action.
Several strategies have been explored to overcome these solubility issues, including the formulation of solid dispersions (SDs) of the drug with hydrophilic carriers. Solid dispersions are one of the most effective methods for improving the solubility and dissolution rate of poorly soluble drugs. Among various carriers, polyvinylpyrrolidone K30 (PVP K30) has been widely used because of its excellent solubilizing properties and compatibility with many drugs.
In this study, two different methods—fusion and solvent evaporation—were used to prepare solid dispersions of lumefantrine. The goal of this research is to enhance the solubility and dissolution rate of lumefantrine, thereby improving its bioavailability.1-3
MATERIALS AND METHODS:
Materials:
Lumefantrine was obtained as a gift sample from Aurobindo Pharma Pvt Ltd, Hyderabad. PVP K30 was purchased from Merck Supplies, Chennai. All other chemicals used in the study were of analytical grade.
Preparation of Solid Dispersions:
Solid dispersions of lumefantrine were prepared using two different methods: the fusion method and the solvent evaporation method.
Fusion Method:
In the fusion method, PVP K30 and lumefantrine were mixed in the desired drug-to-carrier ratio (1:1, 1:2, 1:3) and heated at a temperature of 100°C until a uniform molten mass was obtained. The molten mass was then cooled to room temperature and pulverized.
Solvent Evaporation Method:
For the solvent evaporation method, the drug and PVP K30 (1:1, 1:2, 1:3) were dissolved in a suitable solvent (e.g., ethanol). The solvent was then evaporated under reduced pressure using a rotary evaporator and the resulting solid dispersion was dried at room temperature to remove residual solvent4-6.
Characterization of Solid Dispersions:
The solid dispersions were characterized for the following parameters:
1. Drug Content Determination: The drug content in the solid dispersions was determined by dissolving a known quantity of the formulation in an appropriate solvent and analyzing the drug content spectrophotometrically.
2. Solubility Studies: The solubility of lumefantrine in water was determined by placing a known excess amount of the drug or solid dispersion in 100mL of water and allowing it to equilibrate for 24hours at 37°C. The solubility was then measured using a UV spectrophotometer.
3. In Vitro Dissolution Studies: Dissolution studies were performed using a USP dissolution apparatus II (paddle method). The solid dispersion equivalent to 100mg of lumefantrine was placed in the dissolution vessel containing 900 mL of phosphate buffer (pH 6.8) at 37°C and stirred at 75 rpm. Samples were withdrawn at predetermined intervals and analyzed spectrophotometrically.
4. Fourier Transform Infrared Spectroscopy (FTIR): FTIR spectroscopy was used to identify any potential drug-carrier interactions in the solid dispersion. The FTIR spectra of pure drug, PVP K30, and their solid dispersions were recorded 7-10.
RESULTS AND DISCUSSION:
1. Drug Content:
The drug content in the solid dispersions was found to be consistent across all formulations, with no significant variation between the fusion and solvent evaporation methods. The average drug content ranged between 98% and 102% for all formulations.
2. Solubility Studies:
The solubility of lumefantrine was significantly enhanced in the solid dispersions compared to the pure drug. The maximum solubility was observed in the formulation prepared by the solvent evaporation method with a drug-to-carrier ratio of 1:3, where the solubility was increased by approximately 2-fold compared to pure lumefantrine.
3. In Vitro Dissolution Studies:
The dissolution studies revealed a marked improvement in the dissolution rate of lumefantrine in the solid dispersion formulations. The formulation prepared by the solvent evaporation method (1:3 ratio) exhibited the highest dissolution rate, with over 99% of the drug released within 30 minutes. In contrast, pure lumefantrine showed less than 20% dissolution in the same time frame.
4. Fourier Transform Infrared Spectroscopy (FTIR):
The FTIR spectra of the solid dispersions did not show any significant changes in the characteristic peaks of lumefantrine and PVP K30, indicating no chemical interaction between the drug and the carrier 11-18.
CONCLUSION:
The formulation of lumefantrine solid dispersions using PVP K30 by both the fusion and solvent evaporation methods resulted in significantly improved solubility and dissolution rate compared to pure lumefantrine. Among the two methods, the solvent evaporation method demonstrated superior performance in enhancing drug solubility and dissolution rate. This study highlights the potential of solid dispersions as a promising strategy for improving the bioavailability of lumefantrine and other poorly water-soluble drugs.
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Received on 14.03.2025 Revised on 31.03.2025 Accepted on 16.04.2025 Published on 23.04.2025 Available online from April 26, 2025 Asian J. Pharm. Tech. 2025; 15(2):116-118. DOI: 10.52711/2231-5713.2025.00019 ©Asian Pharma Press All Right Reserved
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