Browsing by Subject "Ubiquinones"
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Item Biopharmaceutical classification and development of limonene-based self-nanoemulsified capsule dosage form of coenzyme Q10(Texas Tech University, 2004-05) Palamakula, AnithaCoenzyme 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.Item Breast Cancer patients' use of coenzyme Q10(Texas Tech University, 2003-05) Jarman, Gina LynnDietary supplement use is common, particularly among cancer patients. Women with breast and gynecological cancers use dietary supplements at higher rates than individuals with other types of cancers. One particular dietary supplement, Coenzyme Q, has been advertised for use among breast cancer patients to increase quality of life, boost the immune system and improve prognosis. To date, no well-controlled, large, clinical trials have researched the results of Coenzyme Q use among breast cancer patients. Despite this fact, some breast cancer patients supplement their diets with Coenzyme Q. Stephen Sapp's Expanded Rational Expectations Intention (EREI) model expanded from Icek Ajzen and Martin Fishbein's Theory of Reasoned Action served as the theoretical model for this study. In the EREI model, the constructs in the EREI model of knowledge, beliefs, referent others, social acceptability, attitude and subjective norm theoretically predict intention. Study subjects were 160 non-metastatic breast cancer patients currently undergoing chemotherapy, radiation therapy or hormonal therapy at Covenant Health System Joe Arrington Cancer Center. Subjects completed a survey with indicators measuring the constructs within the EREI model in order to determine factors that motivate breast cancer subjects whether to supplement with Coenzyme Q. Other questions within the survey assessed whom subjects trust for accurate or reliable dietary supplement information, disclosure with physicians about what dietary supplements they use, where they learn about supplements that they use, and what supplements subjects currently use. PLSPATH is a type of structural equation modeling technique that was used to analyze the data to determine whether the EREI model could predict the intentions of breast cancer subjects to supplement with Coenzyme Q. Results indicated that the EREI model predicted breast cancer subjects' intentions to supplement with Coenzyme Q. Beliefs had a significant effect on attitude, which in turn had a significant effect on intention. Referent others had a significant effect on subjective norm, which in turn had a significant effect on intention. Attitude was a stronger predictor of intention than was subjective norm. Social acceptability and knowledge were not related to intention. Results suggested that; Subjects trust healthcare professionals for dietary supplement information. The majority of subjects disclose dietary supplementation with their physicians. Subjects use a variety of dietary supplements. Caucasian women and women with higher education levels use more dietary supplements than non-Caucasian women and those with lower education levels. Coenzyme Q users use more dietary supplements than non-Coenzyme Q users.Item Eutectic-based self-nanoemulsified drug delivery systems for solid oral dosage forms(Texas Tech University, 2002-08) Nazzal, Sami MahmoudCommercially available nutraceutical preparations suffer from poor compliance with the regulatory guidelines for quality, strength, absorption characteristics, and safety. Preparation of Coenzyme Q[10] (C[0]Q[10]), presents an additional challenge in the development of an oral formulation because of its poor solubility. In recent years lipid-based and self-emulsified formulations gained more attention because of their ability to improve aqueous solubility and bioavailability of a variety of drugs. These formulations, however, suffer from large dosage size exceeding CFR limits for excipients, irreversible crystallization, and excipient interaction with the shell material of the capsules. Reversibly induced re-crystallized semisolid self-nanoemulsifying drug delivery system can be considered as an alternative delivery approach. In this method, the interaction between C0Q10 and a suitable eutectic agent allows the oil phase containing the drug to melt at body temperature from its semisolid consistency and disperse to form emulsion droplets in nanometer size range. C0Q10 was found to form a eutectic mixture with menthol and essential oils, which was demonstrated using binary phase diagrams. This ability of C0Q10 to form eutectic mixture with essential oils was exploited in the development of eutectic-based delivery system for CoQ. At a ratio of 1:1, the mixture of C0Q10 and lemon oil melts at a temperature below 37°C and reversibly re-crystallizes at room temperature improving its shelf life. This was verified by FT-IR and thermal analysis. Upon consumption, C0Q10 blends with surfactant and cosurfactant re-melts and gently emulsifies into a dispersion with nanometer-sized particles. The quality and ease of emulsion formation was monitored by turbidimetiy and dissolution studies, which revealed the distinctive phases of the emulsion disruption process: lag time, pseudolinear phase, and the plateau. Within 15 minutes, eutectic-based formulations completely solubilize into the aqueous dissolution medium. Dissolution lag time was further cortelated with the formation of different liquid crystalline phases at the lipid-water interface during the early stages of the disruption process. Formulation ingredients, polyoxyl 35 castor oil (Cremophor EL), medium-chain mono- and diglycerides (Capmul MCM-C8), and lemon oil were subsequently optimized for release and emulsification rate by applying the Box-Behnken design of experiments. The quadratic interactions between the formulation ingredients were elucidated using contour and response surface plots. Optimized formulation was then incorporated into a tablet dosage form. This was possible as the eutectic-based formulation of C0Q10 forms a wax-like paste when mixed with small quantities of copolyvidone (KoUidon VA 64). Copolyvidone paste ground with maltodextrin produced granules with good flow properties that are readily available for direct compression. When compressed, the above mixture produced soft compacts. Therefore, directly compressible microcrystalline cellulose (MCC) was added at 20% loading. Since Avicel® MCC comes in different grades, Avicel® particle size and moisture content were evaluated for their effect on compaction, surface roughness, and dissolution properties of the self-emulsified solid formulation. Heckel analysis, three point flexure test, and profilometry were applied in the study. Avicel PH-105 demonstrated a sustained release effect with minimum yield and tensile strength. Among the MCC grades, Avicel® PH-112, with an average diameter of 90 ^m and moisture content no more than 1.5%, was selected for the subsequent studies. Solid formulation ingredients, copolyvidone, maltodextrin, and MCC, were then optimized using the Box Behnken design to obtain a level of the ingredients with desired weight, dissolution rate, tensile strength, friability and disintegration. An optimized immediate release formulation was obtained that confined to the dissolution and disintegration limits set forth by USP guidelines. The formulation had a final weight of 867 mgs and a cumulative percent release of 92% in 45 minutes. For final production, process variables including applied compression pressure, amount of silicon dioxide added, and magnesium stearate mixing time were evaluated for their effect on the dissolution behavior of the self-emulsified tablet dosage form. Colloidal silicone dioxide and compression pressure induced a sustained release effect where the lipid formulation was delivered over a time span from 4 to 12 hrs. Process variables were therefore optimized using the face centered cubic design to obtain a final tablet dosage form that delivers the lipid-formulation over 8 hrs with a zero-order release kinetics. The final product had an improved flow ability and compaction properties with a flow index of 87 and a hardness of 5 kg. Optimized formulation was subjected to an accelerated stability study under various light, temperature, and humidity conditions. Low humidity conditions at 25°C and 30°C had an adverse effect on the extent and release rate of the eutectic lipid-based formulation. Dissolution profile was stable for 4 months when the preparations were refrigerated and stored under 60% relative humidity at 25°C and 30°C