Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability

Yeom, Dong Woo; Chae, Bo Ram; Kim, Jin Han; Chae, Jun Soo; Shin, Dong Jun; Kim, Chang‐Hyun; Kim, Dae Jung; Choi, Ji Ho; Song, Seh Hyon; Oh, Dong-Ho; Sohn, Se I.; Choi, Young Wook

doi:10.18632/oncotarget.21691

Cited by 23 publications

(22 citation statements)

References 40 publications

(57 reference statements)

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“…Owing to the homogeneously dispersed oil droplets, in which the drug exists in molecular solubilization, pertinent dissolution could take place. This behavior was consistent with our earlier report that Transcutol ® P-employed S-SuSMED granules and tablets showed a rapid release and a gradually increased release, respectively [15]. Compared with raw VST and Diovan ® , the earlier formulation (Transcutol ® P-employed) increased VST dissolution after 2 h by 2.5-fold and 1.6-fold, whereas the present formulation (GEL-employed) increased the dissolution by 6-fold and 2.3-fold, respectively.…”

Section: Resultssupporting

confidence: 93%

Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire® 44/14

et al. 2019

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To improve the dissolution and oral bioavailability of valsartan (VST), we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMED) composed of Capmul® MCM (oil), Tween® 80 (surfactant), Transcutol® P (cosurfactant), and Poloxamer 407 (precipitation inhibitor) but encountered a stability problem (Transcutol® P-induced weight loss in storage) after solidification. In the present study, replacing Transcutol® P with Gelucire® 44/14 resulted in a novel SuSMED formulation, wherein the total amount of surfactant/cosurfactant was less than that of the previous formulation. Solidified SuSMED (S-SuSMED) granules were prepared by blending VST-containing SuSMED with selective solid carriers, L-HPC and Florite® PS-10, wherein VST existed in an amorphous state. S-SuSMED tablets fabricated by direct compression with additional excipients were sufficiently stable in terms of drug content and impurity changes after 6 months of storage at accelerated conditions (40 ± 2 °C and 75 ± 5% relative humidity). Consequently, enhanced dissolution was obtained (pH 1.2, 2 h): 6-fold for S-SuSMED granules against raw VST; 2.3-fold for S-SuSMED tablets against Diovan® (reference tablet). S-SuSMED tablets increased oral bioavailability in rats (10 mg/kg VST dose): approximately 177–198% versus raw VST and Diovan®. Therefore, VST-loaded S-SuSMED formulations might be good candidates for practical development in the pharmaceutical industry.

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Section: Resultssupporting

confidence: 93%

Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire® 44/14

et al. 2019

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“…Response surface methodologies, such as mixture designs, have recently been used in the formulation of microemulsions (ME) [ 25 , 26 , 27 ], self-emulsifying drug delivery systems (SEDDS) [ 28 , 29 , 30 ], liposomes [ 31 , 32 ] and tablets [ 19 , 33 , 34 , 35 , 36 , 37 , 38 ]. The D-optimal design is one of the most used methodologies in this field, because it allows different composition constraints, in which the sum of all components is constant (100% w / w ).…”

Section: Introductionmentioning

confidence: 99%

“…The D-optimal design is one of the most used methodologies in this field, because it allows different composition constraints, in which the sum of all components is constant (100% w / w ). Secondly, it also estimates the excipients’ effects on the formulation characteristics, thus permitting the optimization of the whole system [ 34 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a Solid Formulation Containing a Microemulsion of a Novel Artemisia Extract with Nematocidal Activity for Oral Administration

et al. 2020

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Background: Intestinal nematode infections are usually treated with benzimidazole drugs, but the emergence of resistance to these drugs has led to an increasing demand of new anthelmintic strategies. A new microemulsion formulation (ME) consisting of an Artemisia absinthium extract with proven nematocidal efficacy was previously developed. The aim of our study is to implement a D-optimal mixture design methodology to increase the amount of a silica material (loaded with this ME) in a tablet formulation, considering its tensile strength and disintegration time. Methods: 16 experiments or combinations of the 6 tablet components (loaded silica, microcrystalline cellulose, polyvinylpyrrolidone, croscarmellose, Syloid® 244 FP and magnesium stearate) were assessed. Tensile strength and disintegration time models were developed, and an optimization process was carried out. Results: Tensile strength was improved by increasing the polyvinylpyrrolidone content, while croscarmellose decreased the disintegration time. The optimized powder mixture contains 49.7% w/w of the loaded silica material. A compression force of 12 kN was applied to the powder mixture to form tablets with a tensile strength of 2.0 MPa and a disintegration time of 3.8 min. Conclusions: Our results show that D-optimal mixture designs provide a promising approach to formulate liquid-loaded silica materials.

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“…To evaluate the flow property of the powder blends and granules, the bulk density and angle of repose were measured as previously reported. 20 Briefly, accurately weighed samples (50 g) were poured into a graduated cylinder, the volume was measured to obtain the apparent bulk density, and the cylinder was tapped 200 times using a tap device (Tap Density 50-1200; Varian Inc., Palo Alto, CA, USA) to obtain the tapped bulk density. Separately, the angle of repose was measured using a device (PTG-S3; Pharma test, Frankfurt, Germany).…”

Section: Methodsmentioning

confidence: 99%

Immediate release tablet formulation of varenicline salicylate and comparative pharmacokinetic study in human volunteers

Kwak¹,

Lee²,

Yoon³

et al. 2018

DDDT

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PurposeTo develop an immediate release-type tablet containing varenicline salicylate (VRC-S), a smoking cessation agent, formulation and stability studies were performed. The in vitro dissolution and in vivo pharmacokinetic (PK) behavior of the tablets were compared with those of the commercial product (Champix) as a reference.Materials and methodsThe characteristics of the powder were investigated by particle morphology, size distribution, solubility, hygroscopicity, differential scanning calorimetry, and powder X-ray diffraction. Based on the drug–excipient compatibility test, different VRC-S tablets were prepared with the selected excipients through direct compression or wet granulation method and subjected to a dissolution test. The stability of the most promising VRC-S tablet (F4) was evaluated under accelerated conditions (40°C and 75% relative humidity). Further, the dissolution and human pharmacokinetic profiles of the F4 tablet and Champix were compared.ResultsVRC-S showed a positively skewed unimodal size distribution with a specific surface area of 2.02 m2/g, single endothermic peak of 225.2°C in differential scanning calorimetry, crystalline internal structure in powder X-ray diffraction, aqueous solubility of 244.7 mg/mL, and hygroscopicity of 0.256 mg/g. The wet granulation method was preferred for tablet preparation and employed the following excipients: microcrystalline cellulose and anhydrous dibasic calcium phosphate as diluents, croscarmellose sodium as a disintegrant, and colloidal silicon dioxide and magnesium stearate as lubricants. The F4 tablet was stable for 6 months under accelerated conditions. The dissolution of VRC was pH independent, revealing f2 values of 76.49 and 68.38 at pH 1.2 and pH 6.8, respectively. After the oral administration of F4 tablet and Champix to healthy human volunteers, pharmacokinetic parameters, including time to reach the maximum plasma concentration (Tmax), maximum plasma concentration (Cmax), and area under the curve from 0 to infinity (AUCinf), were compared. The values of 90% CI were 0.972–1.035 for Cmax and 0.982–1.075 for AUCinf, which was indicative of the bioequivalence of both products.ConclusionVRC-S–containing F4 tablet might be a good candidate for smoking cessation treatment.

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Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability

Cited by 23 publications

References 40 publications

Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire® 44/14

Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire® 44/14

Development of a Solid Formulation Containing a Microemulsion of a Novel Artemisia Extract with Nematocidal Activity for Oral Administration

Immediate release tablet formulation of varenicline salicylate and comparative pharmacokinetic study in human volunteers

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