Formulation design, in vitro characterizations and anti-malarial investigations of artemether and lumefantrine-entrapped solid lipid microparticles.
BACKGROUND
Poor aqueous solubility of artemether and lumefantrine makes it important to seek better ways of enhancing their oral delivery and bioavailability.


OBJECTIVE
To formulate and carry out in vitro and anti-malarial pharmacodynamic evaluations of solidified reverse micellar solutions (SRMS)-based solid lipid microparticles (SLMs) of artemether and lumefantrine for oral delivery and improved bioavailability.


METHODS
Rational blends of Softisan(®)154 and Phospholipon(®)90H lipid matrices, and different concentrations of artemether and lumefantrine were used to formulate several batches of SLMs. Drug-free SLMs were also formulated. Morphology, particle size, encapsulation efficiency (EE%) and pH studies were performed. In vitro release studies were performed in alcoholic buffer, simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) without enzymes. Anti-malarial pharmacodynamic studies were conducted in mice.


RESULTS
Stable, smooth and spherical particles with sizes ranging from 4.2 ± 0.02 to 9.3 ± 0.8 µm were formed. EE% of 92.2-97.3% and 30.2-84.7% and pH of 3.0 ± 0.02 to 4.9 ± 0.12 and 3.0 ± 0.02 to 5.8 ± 0.05 were obtained for artemether and lumefantrine SLMs, respectively. Release of 100, 88.28 and 75.49%, as well as 63.26, 34.31 and 56.17% were recorded for artemether and lumefantrine in alcoholic buffer, SGF and SIF, respectively. Pharmacodynamic studies indicated very significant (p < 0.05) clearance of parasitaemia in plasmodium-infected mice by the drug-loaded SLMs.


CONCLUSIONS
Oral delivery and bioavailability of artemether and lumefantrine could be improved using SRMS-based SLMs.
a Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences , University of Nigeria , Nsukka , Enugu State , Nigeria ;
Chinazom
C
Agbo
b Nanomedicines and Drug Delivery Research Group, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences , Nnamdi Azikiwe University , Awka , Anambra State , Nigeria ;
Chukwuebuka
C
Umeyor
a Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences , University of Nigeria , Nsukka , Enugu State , Nigeria ;
Franklin
F
Kenechukwu
a Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences , University of Nigeria , Nsukka , Enugu State , Nigeria ;
John
J
Ogbonna
c Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences , University of Nigeria , Nsukka , Enugu State , Nigeria.
Salome
S
Chime
a Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences , University of Nigeria , Nsukka , Enugu State , Nigeria ;
Charles
C
Lovelyn
c Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences , University of Nigeria , Nsukka , Enugu State , Nigeria.
Obumneme
O
Agubata
a Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences , University of Nigeria , Nsukka , Enugu State , Nigeria ;
Kenneth
K
Ofokansi
a Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences , University of Nigeria , Nsukka , Enugu State , Nigeria ;
Anthony
A
Attama
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000737:chemistry; D001682:Biological Availability; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004983:Ethanolamines / Q000008:administration & dosage* / Q000737:chemistry; D005449:Fluorenes / Q000008:administration & dosage* / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D000078102:Lumefantrine; D051379:Mice; D008863:Microspheres; D010316:Particle Size; D012995:Solubility
D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D008055:Lipids; D000077549:Artemether; D000078102:Lumefantrine
Drug delivery; Phospholipon®90H; Softisan®154; emulsion congealing; hot homogenization; parasitaemia