Improved solubility, dissolution rate, and oral bioavailability of main biflavonoids from Selaginella doederleinii extract by amorphous solid dispersion

Rivaroxaban (RXB), a novel oral anticoagulant that directly inhibits factor Xa, is a poorly soluble drug belonging to Biopharmaceutics Classification System (BCS) class II. In this study, a hot-melt extruded amorphous solid dispersion (HME-ASD) containing RXB is prepared by changing the drug:polymer ratio (Polyvinylpyrrolidione-vinyl acetate 64, 1:1–1:4) and barrel temperature (200–240 °C), fixed at 20% of Cremophor® RH 40 and 15 rpm of the screw speed, using the hot-melt extruding technique. This study evaluates the solubility, dissolution behavior, and bioavailability for application to oral drug delivery and optimizes the formulation of rivaroxaban amorphous solid dispersion (RXB-ASD). Based on a central composite design, optimized RXB-ASD (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C, Cremophor® RH 40 20%, screw speed 15 rpm) showed satisfactory results for dependent variables. An in vitro drug dissolution study exhibited relatively high dissolution in four media and achieved around an 80% cumulative drug release in 120 min. Optimized RXB-ASD was stable under the accelerated condition for three months without a change in crystallinity and the dissolution rate. A pharmacokinetic study of RXB-ASD in rats showed that the absorption was markedly increased in terms of rate and amount, i.e., the systemic exposure values, compared to raw RXB powder. These results showed the application of quality by design (QbD) in the formulation development of hot-melt extruded RXB-ASD, which can be used as an oral drug delivery system by increasing the dissolution rate and bioavailability.

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Efficient Development of Sorafenib Tablets with Improved Oral Bioavailability Enabled by Coprecipitated Amorphous Solid Dispersion

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2021.121216 ◽

2021 ◽

pp. 121216

Author(s):

Sichen Song ◽

Chenguang Wang ◽

Shan Wang ◽

Ronald A. Siegel ◽

Changquan Calvin Sun

Keyword(s):

Solid Dispersion ◽

Oral Bioavailability ◽

Amorphous Solid ◽

Amorphous Solid Dispersion

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Wetting Kinetics: an Alternative Approach Towards Understanding the Enhanced Dissolution Rate for Amorphous Solid Dispersion of a Poorly Soluble Drug

AAPS PharmSciTech ◽

10.1208/s12249-014-0281-x ◽

2015 ◽

Vol 16 (5) ◽

pp. 1079-1090 ◽

Cited By ~ 20

Author(s):

Sanjay Verma ◽

Varma S. Rudraraju

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Amorphous Solid ◽

Amorphous Solid Dispersion ◽

Enhanced Dissolution ◽

Alternative Approach ◽

Poorly Soluble ◽

Poorly Soluble Drug ◽

Wetting Kinetics

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Optimization of amorphous solid dispersion techniques to enhance solubility of febuxostat

Folia Medica ◽

10.3897/folmed.63.e55838 ◽

2021 ◽

Vol 63 (4) ◽

pp. 557-568

Author(s):

Vaishali P. Patel ◽

Anita P. Patel ◽

Ashish Shah

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Amorphous Solid ◽

Amorphous Powder ◽

Amorphous Solid Dispersion ◽

Scanning Calorimetry ◽

Residual Solvent ◽

Percentage Yield ◽

Poorly Soluble ◽

Powder Characteristics

Febuxostat is a selective inhibitor of xanthine oxidase and belongs to BCS class II drugs having low solubility and high permeability. Solubility is the most important parameter which directly affects dissolution, absorption and bioavailability of the drugs. There are different techniques by which we can improve solubility and dissolution rate of poorly soluble drug. Amorphous solid dispersion is one of the methods which can improve solubility as well as powder characteristics. The aim of the present study was to formulate and optimize various methods of formulating solid dispersion by using various drug-to-polymer ratios and identifying the batch which gives higher solubility as well as amorphous powder of the drug febuxostat. Different techniques like hot melt method, solvent evaporation method and spray drying techniques were selected for optimization. Attempts were made to improve solubility of febuxostat by employing Kolliphor P 188, Kolliphor P 237, Eudragit RLPO in different drug-to-polymer ratios (1:1, 1:1.5, 1:2) as carrier. The prepared solid dispersion was characterized for the saturation solubility, percentage yield, using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powdered X-ray diffraction studies (PXRD), and residual solvent determination. Solid state characterization indicated that febuxostat was present in the amorphous form after mixing with polymeric carrier. In contrast to the pure form of drug, solid dispersion of the drug showed better solubility and amorphous characteristics which can be attributed to decreased crystallinity due to hydrotrophy. Thus, amorphous solid dispersion approach can be used successfully to enhance solubility, dissolution rate and bioavailability of febuxostat.

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Evaluating the effect of the porous and non-porous colloidal silicon dioxide as a stabilizer on amorphous solid dispersion

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i5.4323 ◽

2020 ◽

Vol 10 (5) ◽

pp. 255-263

Author(s):

Smruti P. Chaudhari ◽

Mittal Bhadiyadra ◽

Rutesh H. Dave

Keyword(s):

Silicon Dioxide ◽

Dissolution Rate ◽

Solid Dispersion ◽

Water Solubility ◽

High Surface ◽

Amorphous Solid ◽

Energy System ◽

High Energy ◽

Amorphous Solid Dispersion ◽

The Stability

Advancement in the discovery of drugs has led to many highly lipophilic compounds with very low water solubility. Amorphous solid dispersion is one of the emerging technologies to increase the solubility of these drugs. The stability of these systems is critical since the high energy system tends to recrystallize, which negates the benefits of these systems. In this paper, we are evaluating the use of colloidal silicon dioxide as a potential stabilizer to stabilize the amorphous solid dispersions. Two types of colloidal silicon dioxide are used: porous colloidal silicon dioxide -Syloid 244 Fp and nonporous fumed silica – Aerosil 200. These silicon dioxides have a high surface area. Two methods of incorporation are used to incorporate silicon dioxide into the solid dispersion. The spray drying method is used to make amorphous solid dispersion. It was found that porous silicon dioxide is better to increase stability as well as increasing dissolution rate and % release of the drug. The addition of silicon dioxide internally to the dispersion increases the dissolution rate, and the addition of silicon dioxide externally increases the stability of the solid dispersion. Keywords: colloidal silicon dioxide, stabilizer, amorphous solid dispersion, low water solubility

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