scholarly journals Effect of Surfactants and Polymers on the Dissolution Behavior of Supersaturable Tecovirimat-4-Hydroxybenzoic Acid Cocrystals

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1772
Author(s):  
Yumiao Feng ◽  
Yuanyuan Meng ◽  
Fangyun Tan ◽  
Lin Lv ◽  
Zhiping Li ◽  
...  
Keyword(s):  
Water Soluble ◽  
Poloxamer 407 ◽  
Dissolution Enhancement ◽  
Dissolution Behavior ◽  
Polysorbate 80 ◽  
Poorly Water Soluble Drugs ◽  
Pharmaceutical Cocrystals ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Pvp K30

(1) Background: Pharmaceutical cocrystals have attracted remarkable interest and have been successfully used to enhance the absorption of poorly water-soluble drugs. However, supersaturable cocrystals are sometimes thermodynamically unstable, and the solubility advantages present a risk of precipitation because of the solution-mediated phase transformation (SMPT). Additives such as surfactants and polymers could sustain the supersaturation state successfully, but the effect needs insightful understanding. The aim of the present study was to investigate the roles of surfactants and polymers in the dissolution-supersaturation-precipitation (DSP) behavior of cocrystals. (2) Methods: Five surfactants (SDS, Poloxamer 188, Poloxamer 407, Cremophor RH 40, polysorbate 80) and five polymers (PVP K30, PVPVA 64, HPC, HPMC E5, CMC-Na) were selected as additives. Tecovirimat-4-hydroxybenzoic (TEC-HBA) cocrystals were chosen as a model cocrystal. The TEC-HBA cocrystals were first designed and verified by PXRD, DSC, SEM, and FTIR. The effects of surfactants and polymers on the solubility and dissolution of TEC-HBA cocrystals under sink and nonsink conditions were then investigated. (3) Results: Both the surfactants and polymers showed significant dissolution enhancement effects, and most of the polymers were more effective than the surfactants, according to the longer Tmax and higher Cmax. These results demonstrate that the dissolution behavior of cocrystals might be achieved by the maintained supersaturation effect of the additives. Interestingly, we found a linear relationship between the solubility and Cmax of the dissolution curve for surfactants, while no similar phenomena were found in solutions with polymer. (4) Conclusions: The present study provides a basis for additive selection and a framework for understanding the behavior of supersaturable cocrystals in solution.

scholarly journals Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

Polymers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1679
Author(s):  
Thao T.D. Tran ◽  
Phuong H.L. Tran
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Dissolution Enhancement ◽  
Formulation Development ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Insoluble Polymers

In recent decades, solid dispersions have been demonstrated as an effective approach for improving the bioavailability of poorly water-soluble drugs, as have solid dispersion techniques that include the application of nanotechnology. Many studies have reported on the ability to change drug crystallinity and molecular interactions to enhance the dissolution rate of solid dispersions using hydrophilic carriers. However, numerous studies have indicated that insoluble carriers are also promising excipients in solid dispersions. In this report, an overview of solid dispersion strategies involving insoluble carriers has been provided. In addition to the role of solubility and dissolution enhancement, the perspectives of the use of these polymers in controlled release solid dispersions have been classified and discussed. Moreover, the compatibility between methods and carriers and between drug and carrier is mentioned. In general, this report on solid dispersions using insoluble carriers could provide a specific approach and/or a selection of these polymers for further formulation development and clinical applications.

It is Possible to Achieve Tablets with Good Tabletability from Solid Dispersions – the Case of the High Dose Drug Gemfibrozil

2020 ◽  
Vol 17 ◽  
Author(s):  
Eduarda Rocha Bigogno ◽  
Luciano Soares ◽  
Matheus Henrique Ruela Mews ◽  
Melissa Zétola ◽  
Giovana Carolina Bazzo ◽  
...  
Keyword(s):  
Drug Release ◽  
Dissolution Rate ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Dissolution Enhancement ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Croscarmellose Sodium ◽  
Poorly Water Soluble

Background: Solid dispersions (SDs) have been extensively used to increase dissolution of poorly water-soluble drugs. However, there are few studies exploring SDs properties that must be considered during tablet development, like tabletability. Poorly water-soluble drugs with poor compression properties and high therapeutic doses, like gemfibrozil, are an additional challenge in the production of SDs-based tablets. Objective: This study evaluates the applicability of SDs to improve both tabletability and dissolution rate of gemfibrozil. A SD-based tablet formulation was also proposed. Method: SDs were prepared by ball milling, using hydroxypropyl methylcellulose (HPMC) as carrier, according to a 23 factorial design. The formulation variables were: gemfibrozil:HPMC ratio, milling speed, and milling time. The response in the factorial analysis was the tensile strength of the compacted SDs. Dissolution rate and solid-state characterization of SDs were also performed. Results: SDs showed simultaneous drug dissolution enhancement and improved tabletability when compared to corresponding physical mixtures and gemfibrozil. The main variable influencing drug dissolution and tabletability was the gemfibrozil:HPMC ratio. Tablets containing gemfibrozil-HPMC-SD (1:0.250 w/w) and croscarmellose sodium showed fast and complete drug release while those containing the same SD and sodium starch glycolate exhibited poor drug release due to their prolonged disintegration time. Conclusion: SDs proved to be effective for simultaneously improving tabletability and dissolution profile of gemfibrozil. Tablets containing gemfibrozil-HPMC-SD and croscarmellose sodium as disintegrating agent showed improved drug release and good mechanical strength, demonstrating the potential of HPMC-based SDs to simultaneously overcome the poor dissolution and tabletability properties of this drug.

scholarly journals Preparation of solid dispersion of rutin by spay drying

2019 ◽  
Vol 35 (2) ◽  
Author(s):  
Nguyen Van Khanh ◽  
Ta Thi Thu ◽  
Hoang Anh Tuan
Keyword(s):  
Spray Drying ◽  
Solid Dispersion ◽  
Flow Rate ◽  
Solid Dispersions ◽  
Tween 80 ◽  
Water Soluble ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Pvp K30

Abstract: The poor solubility of rutin leads to poor bioavailability. The present study is aimed to increase the solubility and bioavailability of rutin using solid dispersion technique. The solid dispersions of rutin were prepared by spray-dried method using β-CD, HPMC E6, HPMC E15, PVP K30, SLS, poloxamer 188 and Tween 80 as carriers. The interaction of rutin with the carriers was evaluated by using methods such as dissolved measurement, Fourier-transformation infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The optimization of formulation was carried out by using Central Composite Face design. Independent variables include PVP K30/rutin ratio, Tween 80/rutin ratio, inlet air temperature, and feed flow rate. Dependent variables are the dissolution and product yield. The optimized preparation conditions for rutin solid dispersions were obtained as PVP K30: rutin at a ratio of 5.77, Tween 80: rutin at a ratio of 0.14, inlet temperature of 110.05, flow rate of 1370.9 ml per hour. The results of this study indicate that the solid dispersion of rutin increases significantly the dissolution of rutin in comparison with rutin. The results of the DSC and XRD studies prove the state transition of rutin from crystalline to amorphous. Keywords Rutin, solid dispersion, spray drying, PVP K30, dissolution. References [1] Beatriz Gullón, Thelmo A. Lú-Chau, María Teresa Moreira, Juan M. Lema, Gemman Eibes, Rutin: A review on extraction, identification and purification methods, biological activities and approaches to enhance its bioavailability, Trends in Food Science & Technology 67 (2017) 220-235. https://doi.org/10.1016/j.tifs.2017.07.008.[2] Carla Aparecida Pedriali, Adjaci Uchoa Fernandes, Leandra de Cássia Bernusso, Bronislaw Polakiewicz, The synthesis of a water-soluble derivative of rutin as an antiradical agent, Química Nova 31(8) (2008) 2147-2151. http://dx.doi.org/10.1590/S0100-40422008000800039.[3] Chiou, Win Loung, Riegelman, Sidney, Pharmaceutical applications of solid dispersion systems, Journal of pharmaceutical sciences 60(9) (1971) 1281-1302. https://doi.org/10.1002/jps.2600600902.[4] Xingwang Zhang, Huijie Xing,Yue Zhao, Zhiguo Ma, Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability Enhancement of Poorly Water-Soluble Drugs, Pharmaceutics 10(3) (2018) 1-33. https://doi.org/10.3390/pharmaceutics10030074.[5] Ladan Akbarpour Nikghalb, Gurinder Singh, Gaurav Singh, Kimia Fazaeli Kahkeshan, Solid Dispersion: Methods and Polymers to increase the solubility of poorly soluble drugs, Journal of Applied Pharmaceutical Science 2(10) (2012) 170-175. https://doi.org/10.7324/JAPS.2012.2103.[6] Amrit Paudel, Zelalem Ayenew Worku, Joke Meeus, Sandra Guns, Guy Van den Mooter, Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: formulation and process considerations, International Journal of Pharmaceutics 453(1) (2013) 253-284. https://doi.org/10.1016/j.ijpharm.2012.07.015.[7] P.B. Dalvi, A.B. Gerange, R. IngaleP, Solid dispersion: strategy to enhance solubility, Journal of Drug Delivery & Therapeutics 5(2) (2015) 20-28. https://doi.org/10.22270/jddt.v5i2.1060.[8] Chau Le Ngoc Vo, Chulhun Park, Beom Jin Lee, Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. European Journal of Pharmaceutics and Biopharmaceutics 85(3) (2013) 799-813. https://doi.org/10.1016/j.ejpb.2013.09.007.[9] I.V. Koval’skii, I.I. Krasnyuk, I.I. Krasnyuk, O.I. Nikulina, A.V. Belyatskaya, Yu. Ya. Kharitonov, N.B. Fel’dman, S.V. Lutsenko, V.V. Grikh, Studies of the Solubility of Rutin from Solid Dispersions, Pharmaceutical Chemistry Journal 47(11) (2014) 612-615. https://doi.org/10.1007/s11094-014-1020-z.  

scholarly journals Spray Congealing: An Emerging Technology to Prepare Solid Dispersions with Enhanced Oral Bioavailability of Poorly Water Soluble Drugs

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3471 ◽  
Author(s):  
Serena Bertoni ◽  
Beatrice Albertini ◽  
Nadia Passerini
Keyword(s):  
Oral Bioavailability ◽  
Solid Dispersions ◽  
Emerging Technology ◽  
Water Soluble ◽  
Oral Drug ◽  
Dissolution Enhancement ◽  
Drug Bioavailability ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

The low and variable oral bioavailability of poorly water soluble drugs remains a major concern for the pharmaceutical industry. Spray congealing is an emerging technology for the production of solid dispersion to enhance the bioavailability of poorly soluble drugs by using low-melting hydrophilic excipients. The main advantages are the absence of solvents and the possibility to obtain spherical free-flowing microparticles (MPs) by a relatively inexpensive, simple, and one-step process. This review aims to fully describe the composition, structure, physico-chemical properties, and characterization techniques of spray congealed-formulations. Moreover, the influence of these properties on the MPs performance in terms of solubility and dissolution enhancement are examined. Following, an overview of the different spray congealed systems developed to increase the oral drug bioavailability is provided, with a focus on the mechanisms underpinning the bioavailability enhancement. Finally, this work gives specific insights on the main factors to be considered for the rational formulation, manufacturing, and characterization of spray congealed solid dispersions.

scholarly journals Microfibrous Solid Dispersions of Poorly Water-Soluble Drugs Produced via Centrifugal Spinning: Unexpected Dissolution Behavior on Recrystallization

2017 ◽  
Vol 14 (5) ◽  
pp. 1666-1680 ◽  
Author(s):  
Stefania Marano ◽  
Susan A. Barker ◽  
Bahijja T. Raimi-Abraham ◽  
Shahrzad Missaghi ◽  
Ali Rajabi-Siahboomi ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Water Soluble ◽  
Dissolution Behavior ◽  
Poorly Water Soluble Drugs ◽  
Centrifugal Spinning ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble
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