Solid self-microemulsifying formulation for candesartan cilexetil.
Sparingly, water-soluble drugs such as candesartan cilexetil offer challenges in developing a drug product with adequate bioavailability. The objective of the present study was to develop and characterize self-microemulsifying drug delivery system (SMEDDS) of candesartan cilexetil for filling into hard gelatin capsules. Solubility of candesartan cilexetil was evaluated in various nonaqueous careers that included oils, surfactants, and cosurfactants. Pseudoternary phase diagrams were constructed to identify the self-microemulsification region. Four self-microemulsifying formulations were prepared using mixtures of oils, surfactants, and cosurfactants in various proportions. The self-microemulsification properties, droplet size, and zeta potential of these formulations were studied upon dilution with water. The optimized liquid SMEDDS formulation was converted into free flowing powder by adsorbing onto a solid carrier for encapsulation. The dissolution characteristics of solid intermediates of SMEDDS filled into hard gelatin capsules was investigated and compared with liquid formulation and commercial formulation to ascertain the impact on self-emulsifying properties following conversion. The results indicated that solid intermediates showed comparable rate and extent of drug dissolution in a discriminating dissolution medium as liquid SMEDDS indicating that the self-emulsifying properties of SMEDDS were unaffected following conversion. Also, the rate and extent of drug dissolution for solid intermediates was significantly higher than commercial tablet formulation. The results from this study demonstrate the potential use of SMEDDS as a means of improving solubility, dissolution, and concomitantly the bioavailability.
Nekkanti
Vijaykumar
V
NCE Product Development, Integrated Product Development Organization, Dr Reddy's Laboratories Limited, Innovation Plaza, Bachupally, Qutubullapur, Hyderabad 500072, India.
Karatgi
Pradeep
P
Prabhu
Raghavendra
R
Pillai
Raviraj
R
D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry*; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D016503:Drug Delivery Systems / Q000379:methods*; D009821:Oils / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets; D013777:Tetrazoles / Q000737:chemistry*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004304:Dosage Forms; D009821:Oils; D013501:Surface-Active Agents; D013607:Tablets; D013777:Tetrazoles; C077793:candesartan cilexetil