Page 26 - 2020

Ph.D.
(Pharmacy)
DEVELOPMENT AND EVALUATION OF LIPID
BASED DRUG DELIVERY OF BOSENTAN

Ph.D. Scholar : Varia Umang Rohitkumar
Research Supervisor : Dr. B. G. Prajapati

Regi. No.: 15146021006
Abstract :
To avoid problems of conventional therapy of drug delivery and reduced dose, SR matrix
tablet of Bosentan prepared using lipid base material as matrices. Primary screening of
polymer was done by selecting different lipid base materials like COM, Eudragit RSPO,
PRE, Glycerly mono stearate (GMS) and Cetosteryl alcohol (CA). All the batches
developed by direct compression method. Theoretical drug release pattern was carried
out for dose calculation up to 24 hrs. All the batches were evaluated for hardness,
variation in weight, thickness and friability (Physicochemical parameters). FTIR study and
In vitro drug release performed along with experimental design. From the drug release
profile, COM (F1) showed batter retardant effect and PRE (F2) showed effective burst
release. Remaining formulations (F3-F5) were not able to release the drug as per
theoretical drug release profile. After selecting lipid matrices it was optimized by 32 full
factorial design by applying analysis of variance (ANOVA). Concentration of Compritol
and Precirol were selected as an independent factor while time require for 20% drug
release (Y1) and time require for 80% drug release (Y2) were selected as response.
Optimized batch showed drug release 99.45% at 24 hrs with desire burst release.
Pharmacokinetic study displayed exact fit model is Higuchi model having R2 value
0.9886. Combination of two lipid base material PRE and COM exhibit most desire
sustained release as compare to individual.

Bosentan loaded nanostructured lipid carriers (NLCs) developed by hot homogenization
technique using high-speed homogenization along with ultra-sonication. Optimization
done by response surface methodology to identify the influence of solid to liquid lipid
ratio (X1) and surfactant strength (X2) on the particle size (Y1) and drug loading (Y2).
From the pre-formulation study, Transcutol HP, Poloxamer 188 and PRE elected as a
liquid lipid, surfactant and solid lipid respectively. Optimize formula having solid to liquid
lipid ratio (85:15) %w/w and surfactant strength 1% w/v. Final formulation contained
particle size 144.5±0.34 nm (n=3), surface charge -36.6 mv and 90.89±0.10 % (n=3) drug
entrapment. Characterization performed using DSC, FTIR and TEM analysis. The
Haemolytic study carried out to check blood compatibility. In- Vitro and Ex -Vivo drug
release study showed 93.36% and 88.87 %, respectively after 24 hours. In-vivo
performance was conducted on wistar albino rats. As per the result of in-vivo study
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