Optimization of amorphous solid dispersion techniques to enhance solubility of febuxostat

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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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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Preparation and Characterization of Artemether Solid Dispersion by Spray Drying Technique

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v11i2.4557 ◽

2021 ◽

Vol 11 (2) ◽

pp. 1-5

Author(s):

Dhiraj Dabhade ◽

Kamlesh Wadher ◽

Shrikant Bute ◽

Nikita Naidu ◽

Milind Umekar ◽

...

Keyword(s):

Dissolution Rate ◽

Spray Drying ◽

Solid Dispersion ◽

Solid Dispersions ◽

Amorphous Solid ◽

Study Data ◽

Water Soluble ◽

Amorphous Solid Dispersion ◽

Scanning Calorimetry ◽

Poorly Water Soluble

Introduction: Artemether, a BCS class IV drug (poorly water soluble and poorly permeable, less bioavailability) but is found to be effective against falciparum malaria. Preparation of water soluble formulation could be the technique to improve bioavailability of such drug. The most ideally used technique to enhance the solubility and dissolution of poorly water soluble drugs is Solid dispersion method. Method: The objective of the study was to enhance the solubility and dissolution rate of Artemether by preparing solid dispersions using Soluplus, at different ration of 1:1, 1:2, 1:3 and 1:4 using spray drying technology. Prepared Solid dispersions were characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Results: The spray-dried solid dispersions found to be having less crystallinity and showed higher dissolution rates. Solubility study data showed the optimum drug/Soluplus ratio to be 1:3. The dissolution studies of Solid dispersions in 1.2 pH and 6.8 pH buffer showed higher drug release as compared to pure drug. Conclusion: Thus we conclude that an amorphous solid dispersion of Artemether could be a better option for enhancing the dissolution rate of drug Keywords: solid dispersion, artemether, soluplus, solubility enhancement

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Impact of Drug-Polymer Interaction in Amorphous Solid Dispersion Aiming for the Supersaturation of Poorly Soluble Drug in Biorelevant Medium

AAPS PharmSciTech ◽

10.1208/s12249-020-01737-6 ◽

2020 ◽

Vol 21 (5) ◽

Author(s):

Cassiana Mendes ◽

Rafael G. Andrzejewski ◽

Juliana M. O. Pinto ◽

Leice M. R. de Novais ◽

Andersson Barison ◽

...

Keyword(s):

Solid Dispersion ◽

Amorphous Solid ◽

Amorphous Solid Dispersion ◽

Poorly Soluble ◽

Poorly Soluble Drug ◽

Drug Polymer Interaction ◽

Biorelevant Medium ◽

Polymer Interaction

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The Development and Optimization of Hot-Melt Extruded Amorphous Solid Dispersions Containing Rivaroxaban in Combination with Polymers

Pharmaceutics ◽

10.3390/pharmaceutics13030344 ◽

2021 ◽

Vol 13 (3) ◽

pp. 344

Author(s):

Jong-Hwa Lee ◽

Hyeong Sik Jeong ◽

Jong-Woo Jeong ◽

Tae-Sung Koo ◽

Do-Kyun Kim ◽

...

Keyword(s):

Drug Delivery ◽

Dissolution Rate ◽

Solid Dispersion ◽

Oral Drug Delivery ◽

Amorphous Solid ◽

Drug Dissolution ◽

Oral Drug ◽

Amorphous Solid Dispersion ◽

Screw Speed ◽

Hot Melt

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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Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502016000100002 ◽

2016 ◽

Vol 52 (1) ◽

pp. 1-13 ◽

Cited By ~ 6

Author(s):

Ehsan Adeli

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Water Soluble ◽

Polyethylene Glycols ◽

X Ray Diffraction ◽

Drug Release Profile ◽

Scanning Calorimetry ◽

Peg 4000 ◽

Poorly Soluble

ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin), various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG). Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR) spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Election Microscopy (SEM). In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000.

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Solvent-free direct formulation of poorly-soluble drugs to amorphous solid dispersion via melt-absorption

Advanced Powder Technology ◽

10.1016/j.apt.2017.02.020 ◽

2017 ◽

Vol 28 (5) ◽

pp. 1316-1324 ◽

Cited By ~ 10

Author(s):

Shou-Cang Shen ◽

Wai Kiong Ng ◽

Jun Hu ◽

Kumaran Letchmanan ◽

Junwei Ng ◽

...

Keyword(s):

Solid Dispersion ◽

Amorphous Solid ◽

Solvent Free ◽

Amorphous Solid Dispersion ◽

Poorly Soluble Drugs ◽

Poorly Soluble

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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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Impact of HPMCAS on the Dissolution Performance of Polyvinyl Alcohol Celecoxib Amorphous Solid Dispersions

Pharmaceutics ◽

10.3390/pharmaceutics12060541 ◽

2020 ◽

Vol 12 (6) ◽

pp. 541 ◽

Cited By ~ 3

Author(s):

Marius Monschke ◽

Karl G. Wagner

Keyword(s):

Polyvinyl Alcohol ◽

Dissolution Rate ◽

Solid Dispersions ◽

Amorphous Solid ◽

Scanning Calorimetry ◽

Amorphous Solid Dispersions ◽

Dissolution Studies ◽

Rapid Dissolution ◽

Poorly Soluble ◽

Inhibitory Potential

Amorphous solid dispersions (ASDs) have been proven to increase the bioavailability of poorly soluble drugs. It is desirable that the ASD provide a rapid dissolution rate and a sufficient stabilization of the generated supersaturation. In many cases, one polymer alone is not able to provide both features, which raises a need for reasonable polymer combinations. In this study we aimed to generate a rapidly dissolving ASD using the hydrophilic polymer polyvinyl alcohol (PVA) combined with a suitable precipitation inhibitor. Initially, PVA and hydroxypropylmethylcellulose acetate succinate (HPMCAS) were screened for their precipitation inhibitory potential for celecoxib in solution. The generated supersaturation in presence of PVA or HPMCAS was further characterized using dynamic light scattering. Binary ASDs of either PVA or HPMCAS (at 10% and 20% drug load) were prepared by hot-melt extrusion and solid-state analytics were conducted using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and fourier-transformed infrared spectroscopy (FT-IR). The non-sink dissolution studies of the binary ASDs revealed a high dissolution rate for the PVA ASDs with subsequent precipitation and for the HPMCAS ASDs a suppressed dissolution. In order to utilize the unexploited potential of the binary ASDs, the PVA ASDs were combined with HPMCAS either predissolved or added as powder and also formulated as ternary ASD. We successfully generated a solid formulation consisting of the powdered PVA ASD and HPMCAS powder, which was superior in monophasic non-sink dissolution and biorelevant biphasic dissolution studies compared to the binary and ternary ASDs.

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