Biopharmaceutical classification and development of limonene-based self-nanoemulsified capsule dosage form of coenzyme Q10

DSpace/Manakin Repository

Biopharmaceutical classification and development of limonene-based self-nanoemulsified capsule dosage form of coenzyme Q10

Show simple item record


dc.creator Palamakula, Anitha
dc.date.available 2011-02-18T20:50:35Z
dc.date.issued 2004-05
dc.identifier.uri http://hdl.handle.net/2346/14856 en_US
dc.description.abstract Coenzyme QIO (CoQ) is a challenging micronutrient for oral formulation due to its low aqueous solubility and bioavailability. The present dissertation deals with a systematic approach to classify CoQ biopharmaceutically according to FDA biopharmaceutical classification system (BCS), and to develop a self-nanoemulsified capsule dosage form (SNCDF) with chiral limonenes. We have hypothesized that the oral bioavailability of CoQ may be enhanced by limonene based SNCDF. In vitro transport studies using Caco-2 cells and solubility studies indicated that CoQ is moderately permeable and has low solubility. However, CoQ exhibits substantial solubility in limonenes. The permeability of CoQ across isolated rat GI segments revealed regional differences with maximum absorption through duodenum. Based on these results, a limonene based self-nanoemulsified formulation of CoQ was prepared and evaluated by in vitro and in vivo methods. Dissolution studies in water have shown CoQ release of > 90% within 5 minutes. Thermal analysis showed no significant change in CoQ endotherm. FT-IR and X-ray diffraction studies revealed the preservation of CoQ structure, indicating no interactions. Particle size, turbidity and zeta potential measurements have indicated that R-(+)-limonene provided superior self-nanoemulsified formulation of CoQ when compared with S-(-)-limonene. A three-factor, three-level optimization design was used to evaluate the effect of critical process variables on the drug release characteristics. Mathematical relationships, contour plots and response surface methodology were employed with constrained optimization to predict levels of factors that provide maximum drug release. The predicted and observed responses were in good agreement. The long term stability of the formulation was ascertained by subjecting to various temperature and humidity conditions for 6 months. The results indicated no significant effect on turbidity, particle size, zeta potential, DSC, FT-IR and total drug release at room temperature. The in vivo performance of CoQ limonene based SNCDF and eutectic based self-nanoemulsified drug delivery systems (SNEDDS) was evaluated by assessing the pharmacokinetic parameters, Tmax, Cmax, and AUC in rats. The oral bioavailability of SNCDF and SNEDDS was found to increase by 650% and 730% respectively when compared with CoQ powder (control). Preliminary assessment in human volunteers indicated increased tendency of rate and extent and metabolism of nanoemulsified preparations as compared to control.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Texas Tech University en_US
dc.subject Ubiquinone -- pharmacokinetics en_US
dc.subject Nanotechnology en_US
dc.subject Dosage Forms en_US
dc.subject Excipients en_US
dc.subject Terpenes en_US
dc.subject Microstructure en_US
dc.subject Drug Delivery Systems en_US
dc.subject Emulsions en_US
dc.subject Capsules en_US
dc.subject Ubiquinones en_US
dc.subject Pharmacokinetics en_US
dc.subject Drugs -- Dosage -- Design en_US
dc.title Biopharmaceutical classification and development of limonene-based self-nanoemulsified capsule dosage form of coenzyme Q10
dc.type Dissertation
thesis.degree.name Ph.D.
thesis.degree.level Doctoral
thesis.degree.discipline Accounting and Information Systems
thesis.degree.grantor Texas Tech University
thesis.degree.department Pharmaceutical Sciences
dc.degree.department Accounting and Information Systems en_US
dc.rights.availability Unrestricted.

Files in this item

Files Size Format View
31295019466522.pdf 10.89Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

Browse

My Account