Solubilized formulation of olmesartan medoxomil for enhancing oral bioavailability

Lee, Bong Sang; Kang, Myung Joo; Choi, Woo Sik; Choi, Yoon Bae; Kim, Hyung Soo; Lee, Sang Kil; Lee, Jaehwi; Choi, Young Wook

doi:10.1007/s12272-009-2117-x

Cited by 37 publications

(12 citation statements)

References 24 publications

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“…The plasma theophylline level peaked 8 h after oral administration of the formulation, and then slowly declined up to 24 h. The AUC (0-24 h) and AUC (0-¥) were 405 and 415 µg mL -1 h -1 , respectively, and were found to be significantly (p < 0.05) higher than the corresponding values (296.10 and 297.10 µg mL -1 h -1 , respectively) for the commercial product. Although it has been suggested that dissolution of tablets is almost always the rate-limiting step for intestinal absorption (16), this holds for well water soluble and permeable drugs. Dissolution of the drug from tablets controls the pharmacokinetics in case of drugs that fall under the biopharmaceutic classification system (BCS) 1 and 2; BCS 4 drugs possibly depend on dissolution and/or permeability constants.…”

Section: Bioavailability In Rabbitsmentioning

confidence: 99%

Eudraginated polymer blends: A potential oral controlled drug delivery system for theophylline

Emeje¹,

John-Africa²,

Isimi³

et al. 2012

Acta Pharmaceutica

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Sustained release (SR) dosage forms enable prolonged and continuous deposition of the drug in the gastrointestinal (GI) tract and improve the bioavailability of medications characterized by a narrow absorption window. In this study, a new strategy is proposed for the development of SR dosage forms for theophylline (TPH). Design of the delivery system was based on a sustained release formulation, with a modified coating technique and swelling features aimed to extend the release time of the drug. Different polymers, such as Carbopol 71G (CP), sodium carboxymethylcellulose (SCMC), ethylcellulose (EC) and their combinations were tried. Prepared matrix tablets were coated with a 5 % (m/m) dispersion of Eudragit (EUD) in order to get the desired sustained release profile over a period of 24 h. Various formulations were evaluated for micromeritic properties, drug concentration and in vitro drug release. It was found that the in vitro drug release rate decreased with increasing the amount of polymer. Coating with EUD resulted in a significant lag phase in the first two hours of dissolution in the acidic pH of simulated gastric fluid (SGF) due to decreased water uptake, and hence decreased driving force for drug release. Release became faster in the alkaline pH of simulated intestinal fluid (SIF) owing to increased solubility of both the coating and matrixing agents. The optimized formulation was subjected to in vivo studies in rabbits and the pharmacokinetic parameters of developed formulations were compared with the commercial (Asmanyl ® ) formulation. Asmanyl ® tablets showed faster absorption (t max 4.0 h) compared to the TPH formulation showing a t max value of 8.0 h. The C max and AUC values of TPH formulation were significantly (p < 0.05) higher than those for Asmanyl ® , revealing relative bioavailability of about 136.93 %. Our study demonstrated the potential usefulness of eudraginated polymers for the oral delivery of the sparingly soluble drug theophylline.

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Section: Bioavailability In Rabbitsmentioning

confidence: 99%

Eudraginated polymer blends: A potential oral controlled drug delivery system for theophylline

Emeje¹,

John-Africa²,

Isimi³

et al. 2012

Acta Pharmaceutica

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“…Several approaches were investigated to improve the oral bioavailability of OLM, including the development of solid lipid nanoparticles 8 , freezedried solid dispersions 9 , nanosuspensions 10 , nanoemulsions 11 -13 , and self-micro emulsifying drug delivery systems 14 , and solid selfnanoemulsifying drug delivery systems 15 .…”

Section: Introductionmentioning

confidence: 99%

“…These systems can form fine O/W microemulsion droplets (less than 100nm) upon mild agitation and dilution in aqueous media like gastrointestinal fluids. The importance of these systems results from the resultant small droplet size and large surface area; allowing for the enhanced absorption of lipophilic drugs, like OLM, by opening tight junctions to allow Para cellular transport, increasing membrane fluidity to facilitate transcellular absorption, and inhibiting efflux pumps like P-glycoprotein 14,16,17 . Like Nano emulsions, self-nanoemulsifying drug delivery systems (SNEDDS) can be formulated with little energy input (heat or mixing) 18 .…”

Section: Introductionmentioning

confidence: 99%

Untitled

2018

IJPSR

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ABSTRACT:Olmesartan medoxomil (OLM) is a lipophilic (log P = 4.31) antihypertensive drug suffering from limited oral bioavailability in humans (26%) due to its low aqueous solubility, uncontrolled enzymatic conversion to the active metabolite (Olmesartan; OL) and efflux by drug resistance pumps. Surmounting such limitations via incorporation of OLM into selfnanoemulsifying drug delivery systems (SNEDDS). Based on OLM-equilibrium solubility studies in various oils, surfactants and co-surfactants, Capmul ® MCM, Tween ® 20, Cremophor ® EL and polyethylene glycol -400 (PEG) were combined in different ratios to plot ternary phase diagrams. OLM-loaded SENDDS were developed and evaluated forparticle size, polydispersity index (PDI), zeta potential, self-emulsification time, morphology, drug released percentages after 5-min (Q 5min %), 1 hour (Q 1h %) and dissolution efficiency percentages (DE 1h %). The OL pharmacokinetics from SNEDDS (F6) and Benicar ® tablets were evaluated (LC-MS/MS) in rabbits. Spherical OLM-loaded SNEDDS were developed. The best-achieved SNEDDS (F6) showed short emulsification time (13 s), fine droplet size (60.00nm), low PDI (0.25), negative zeta potential (-14.4mV), promising dissolution parameters; Q 5min % (29.78%), Q 1h % (66.69%) and DE 1h % (47.96%) and enhanced in vivo absorption characteristics; shorter T max , higher C max and larger AUC (0−48h ; suggesting its potential for the enhancement of the oral absorption of practically insoluble drugs; like OLM.

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“…OLM has been formulated as a self-microemulsifying drug delivery system (SMEDDS) using capryol 90, tween 20 and tetraglycol (10:60:30, v/v/v) and Lee and his coworkers reported an improved relative bioavailability of 170% compared to the suspension in male Sprague-Dawley rats (11). SMEDDS as a delivery system have been reported to employ high concentration (30-60%) of surfactants that may lead to cellular toxicity (12).…”

Section: Introductionmentioning

confidence: 99%

Product Development Studies on Surface-Adsorbed Nanoemulsion of Olmesartan Medoxomil as a Capsular Dosage Form

2012

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Abstract. The present study aimed at development of capsular dosage form of surface-adsorbed nanoemulsion (NE) of olmesartan medoxomil (OLM) so as to overcome the limitations associated with handling of liquid NEs without affecting their pharmaceutical efficacy. Selection of oil, surfactant, and cosurfactant for construction of pseudoternary phase diagrams was made on the basis of solubility of drug in these excipients. Rationally selected NE formulations were evaluated for percentage transmittance, viscosity, refractive index, globule size, zeta potential, and polydispersity index (PDI). Formulation (F3) comprising of Capmul MCM® (10% v/v), Tween 80® (11.25% v/v), polyethylene glycol 400 (3.75% v/v), and double-distilled water (75% v/v) displayed highest percentage cumulative drug release (%CDR; 96.69± 1.841), least globule size (17.51±5.87 nm), low PDI (0.203±0.032), high zeta potential (−58.93±0.98 mV), and hence was selected as the optimized formulation. F3 was adsorbed over colloidal silicon dioxide (2 ml/400 mg) to produce free-flowing solid surface-adsorbed NE that presented a ready-to-fill capsule composition. Conversion of NE to surface-adsorbed NE and its reconstitution to NE did not affect the in vitro release profile of OLM as the similarity factor with respect to NE was found to be 66% and 73% respectively. The %CDR after 12 h for optimized NE, surface-adsorbed NE, and reconstituted NE was found to be 96.69±0.54, 96.07±1.76, and 94.78±1.57, respectively (p>0.05). The present study established capsulated surfaceadsorbed NE as a viable delivery system with the potential to overcome the handling limitations of NE.

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Solubilized formulation of olmesartan medoxomil for enhancing oral bioavailability

Cited by 37 publications

References 24 publications

Eudraginated polymer blends: A potential oral controlled drug delivery system for theophylline

Eudraginated polymer blends: A potential oral controlled drug delivery system for theophylline

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Product Development Studies on Surface-Adsorbed Nanoemulsion of Olmesartan Medoxomil as a Capsular Dosage Form

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