Improved Oral Absorption of Enteric Coprecipitates of a Poorly Soluble Drug

Kondo, Nobuo; Iwao, Toro; Hirai, Kenichi; Fukuda, Motoko; Yamanouchi, Kouichi; Yokoyama, Kazumasa; Miyaji, Mikio; Ishihara, Yoshiaki; Kon, Kenji; Ogawa, Yasuo; Mayumi, Tadanori

doi:10.1002/jps.2600830425

Cited by 43 publications

(17 citation statements)

References 14 publications

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“…This due to faster precipitation of the polymer around the drug in higher polymer/solvent concentrations. The fast polymer precipitation due to rapid acetone evaporation led to higher drug content and decreases the diffusion of the drug in the external phase identical results were gained by Kondo et al [46]. The low drug release rate could be also attributed to the decrease in a number of pores at MS surface at a higher polymer to drug ratios or an increase of internal phase viscosity [47].…”

Section: In Vitro Release Studysupporting

confidence: 69%

Preparation and Evaluation of 5-Fluorouracil Loaded Microsponges for Treatment of Colon Cancer

Othman¹,

Zayed²,

El‐Sokkary³

et al. 2017

J Cancer Sci Ther

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5-Fluorouracil (5-FU) has a wide anticancer activity versus several types of solid tumors. The activity of 5-FU can be improved and its toxicity can be diminished by enhancing the relative specific accumulation in the tumor regions. The aim of this work was to develop Eudragit RS100 based 5-FU microsponges (MS) for treatment of colon cancer. Oil in oil emulsion solvent diffusion method was used for the preparation of 5-FU sustained release Eudragit RS100 MS. MS were characterized for their encapsulation efficiency, production yield, drug polymer interaction and drug release profiles. Shape, surface morphology visualized by scanning electron microscope (SEM) and particle size of MS was investigated using laser light scattering technique and. Eventually, HCT 116 and CACO2 cell lines were used for determination of cell viability by MTT assay. The results showed that all prepared MS were spherical in shape with several pores on their surfaces. The production yield was in (62.76% ±1.06% and 93.80% ± 1.75%), encapsulation efficiency was in (71.80% ± 1.62% and 101.3% ± 2.60%) and particle size was in ( 53.11 µm ± 41.03 nm and 118.12 µm ± 48.21 nm). Fourier transform infrared revealed that there is no chemical interaction between 5-FU and Eudragit RS100. MS loaded 5-FU was more effective than 5-FU itself as shown by cell viability assay. The results demonstrated that 5-FU with Eudragit RS100 was successfully formulated as sustained release manner and could be a substitution delivery method of 5-FU for oral anticancer treatment.represent an important factor to oral as compared to administration intravenously as reported previously [9].Conversely, intravenous administration of 5-FU yields severe systemic toxic effects of gastrointestinal (GIT), blood complaints, and skin diseases, due to the 5-FU cytotoxicity on healthful human cells. Hence, the need to formulate targeted delivery of 5-FU through oral route would not only diminish the exposure of healthy cells to the drug but also provide an efficient and harmless curative effect for colon cancer with a lower dose and reduced duration of therapy [5]. It was reported that the therapeutic effect of 5-FU can be augmented and its harmful effects can be suppressed by the precise accumulation of the anticancer agent in the tumor regions with continued exposure of the cells to this drug [10]. To extend the exposure time of cancer cells to 5-FU, the drug delivery was formulated by incorporation into microsponge formulation.Microsponges (MS) are micro-sized particles with high porosity and unique ability for encapsulation of a wide multiplicity of pharmaceutical active ingredients. MS delivery system is used to target and modify the release of active ingredients from pharmaceutical formulations, enhance the stability and decrease the side effects [11]. MS have high load activity reach up to 90% entrapment efficiency [12], self-sterilizing Citation: Othman MH, Zayed GM, El-Sokkary GH, Ali UF, Abdellatif AAH (2017) Preparation and Evaluation of 5-Fluorouracil Loaded Microsp...

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Section: In Vitro Release Studysupporting

confidence: 69%

Preparation and Evaluation of 5-Fluorouracil Loaded Microsponges for Treatment of Colon Cancer

Othman¹,

Zayed²,

El‐Sokkary³

et al. 2017

J Cancer Sci Ther

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“…SUBA-itraconazole had a relative bioavailability of 173% (95% CI, 156 to 190%) compared to that of Sporanox. Thus, a 58-mg (42)(43)(44). In one study, Kohri et al (42) evaluated the use of a solid dispersion system with a pHdependent polymeric carrier (hypromellose/hypromellose phthalate) to improve oral bioavailability of albendazole, a poorly water-soluble weakly basic drug with a pH solubility profile similar to that of itraconazole.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic Modeling of Itraconazole and Hydroxyitraconazole for Oral SUBA-Itraconazole and Sporanox Capsule Formulations in Healthy Subjects in Fed and Fasted States

Abuhelwa

Foster

Mudge

et al. 2015

Antimicrob Agents Chemother

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bItraconazole is an orally active antifungal agent that has complex and highly variable absorption kinetics that is highly affected by food. This study aimed to develop a population pharmacokinetic model for itraconazole and the active metabolite hydroxyitraconazole, in particular, quantifying the effects of food and formulation on oral absorption. Plasma pharmacokinetic data were collected from seven phase I crossover trials comparing the SUBA-itraconazole and Sporanox formulations of itraconazole. First, a model of single-dose itraconazole data was developed, which was then extended to the multidose data. Covariate effects on itraconazole were then examined before extending the model to describe hydroxyitraconazole. The final itraconazole model was a 2-compartment model with oral absorption described by 4-transit compartments. Multidose kinetics was described by total effective daily dose-and time-dependent changes in clearance and bioavailability. Hydroxyitraconazole was best described by a 1-compartment model with mixed first-order and Michaelis-Menten elimination for the single-dose data and a time-dependent clearance for the multidose data. The relative bioavailability of SUBA-itraconazole compared to that of Sporanox was 173% and was 21% less variable between subjects. Food resulted in a 27% reduction in bioavailability and 58% reduction in the transit absorption rate constant compared to that with the fasted state, irrespective of the formulation. This analysis presents the most extensive population pharmacokinetic model of itraconazole and hydroxyitraconazole in the literature performed in healthy subjects. The presented model can be used for simulating food effects on itraconazole exposure and for performing prestudy power analysis and sample size estimation, which are important aspects of clinical trial design of bioequivalence studies. Itraconazole is a broad-spectrum orally active triazole antifungal used for both prophylaxis and treatment of systemic fungal infections (1, 2). Itraconazole exerts antifungal activity through the inhibition of fungal cytochrome P450 (CYP) 3A isoenzymes, which mediate the synthesis of ergosterol, a vital component of the fungal cell membrane (3). Itraconazole undergoes extensive hepatic metabolism by human CYP3A4 isoenzymes. Both itraconazole and its major active metabolite, hydroxyitraconazole, inhibit mammalian CYP3A4, although to a lesser extent than that with the fungal CYP3A isoenzymes (4).Itraconazole is currently available as oral capsules in two marketed formulations: Sporanox, the brand product (Janssen Pharmaceuticals, Inc.[5]), and SUBA-itraconazole, the alternative product. SUBA-itraconazole is a novel formulation containing a solid dispersion of itraconazole in a pH-dependent polymeric matrix to enhance its dissolution and intestinal absorption; therefore, it exhibits greater bioavailability than the innovator product. As of 30 June 2015, SUBA-itraconazole has marketing approval in Australia, Spain, Germany, Sweden, and United Kingdom; currently, it is ava...

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“…In one such study, Kondo et al evaluated coprecipitate solid dispersion systems with pH-independent polymeric carriers (povidone (PVP) and copolyvidone) as well as a pH-dependant polymeric carrier [hypromellose phthalate (HP-55)] as a means of improving the bioavailability of the anticancer drug HO-221 (11). In vivo studies conducted with these formulations revealed that absorption of HO-221 achieved with the HP-55 formulation was twice that of the PVP and copolyvidone co-precipitates.…”

Section: Introductionmentioning

confidence: 99%

Targeted Intestinal Delivery of Supersaturated Itraconazole for Improved Oral Absorption

et al. 2008

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Improved Oral Absorption of Enteric Coprecipitates of a Poorly Soluble Drug

Cited by 43 publications

References 14 publications

Preparation and Evaluation of 5-Fluorouracil Loaded Microsponges for Treatment of Colon Cancer

Preparation and Evaluation of 5-Fluorouracil Loaded Microsponges for Treatment of Colon Cancer

Population Pharmacokinetic Modeling of Itraconazole and Hydroxyitraconazole for Oral SUBA-Itraconazole and Sporanox Capsule Formulations in Healthy Subjects in Fed and Fasted States

Targeted Intestinal Delivery of Supersaturated Itraconazole for Improved Oral Absorption

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