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 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.

Surface Solid Dispersion – A Review

2013 ◽  
Vol 6 (1) ◽  
pp. 1915-1925
Author(s):  
Sadhna Khatry ◽  
Neha Sood ◽  
Sandeep Arora
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
High Surface ◽  
High Surface Area ◽  
Water Soluble ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Insoluble Drugs ◽  
Poorly Water Soluble

Preparation of an effective formulation of poorly water-soluble drugs is a key challenge in pharmaceutical technology. Dissolution rate and solubility are the rate- limiting steps for increasing the bioavailability of poorly water‐soluble drugs. Solid dispersion is an efficient technique for improving dissolution rate and subsequently, the bioavailability of poorly water‐soluble drugs. Surface sSolid dDispersion is a novel technique of solid dispersion for dispersing one or more active ingredients on a water insoluble carrier of high surface area in order to achieve increased dissolution rates and bioavailability of insoluble drugs. The Vvarious polymers used in this technique are Avicel, Crosspovidone, sSodium starch glycolate, pPregelatinized starch, Cab-o-sil, Ac-di-sol, KyronT-314, Primojel and pPotato sStarch. This article reviews the various methods of preparation and characterization of surface solid dispersion and compiles some of the drugs formulated as surface solid dispersions. Some of the practical aspects to be considered for preparing surface solid dispersion are selection of a suitable carrier and method of preparation of surface solid dispersion.

Modulation of Drug Crystallization and Molecular Interactions by Additives in Solid Dispersions for Improving Drug Bioavailability

2019 ◽  
Vol 25 (18) ◽  
pp. 2099-2107 ◽  
Author(s):  
Phuong H.L. Tran ◽  
Wei Duan ◽  
Beom-Jin Lee ◽  
Thao T.D. Tran
Keyword(s):  
Solid Dispersion ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Drug Bioavailability ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Potential Applications ◽  
Poorly Water Soluble ◽  
The Right

Background:: An increase in poorly water-soluble drugs makes the design of drug delivery systems challenging. Methods:: Currently, a number of prospective solid dispersions have been investigated with potential applications for delivering a variety of poorly water-soluble drugs. A number of traditional solid dispersions and modifiedsolid dispersions offer attractive advantages in the fabrication, design and development of those drugs for effective therapeutics. Results:: Although traditional solid dispersions can produce a higher release rate, resulting in higher bioavailability compared to conventional dosage forms, this method is not always a promising approach. Modified-solid dispersion has demonstrated both the ability of its polymers to transform drug crystals into amorphous forms and molecular interactivity, thereby improving drug dissolution rate and bioavailability, especially with tough drugs. However, the classification of modified-solid dispersion, which guides the selection of the right strategy in solid dispersion preparation, remains ill-defined. Conclusions:: This review focused on effective strategies in using additives in solid dispersion for improving drug bioavailability.

Fast-dissolving Solid Dispersions for the Controlled Release of Poorly Water-soluble Drugs

2020 ◽  
Vol 26 ◽  
Author(s):  
Phuong H.L. Tran ◽  
Beom-Jin Lee ◽  
Thao T.D. Tran
Keyword(s):  
Drug Delivery ◽  
Controlled Release ◽  
Oral Drug Delivery ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Oral Drug ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

: Solid dispersions offer many advantages for oral drug delivery of poorly water-soluble drugs over other systems, including an increase in drug solubility and drug dissolution. The improvement of drug absorption and higher bioavailability of active pharmaceutical ingredients in the gastrointestinal tract have been reported in various studies. In certain circumstances, a rapid pharmacological effect is required for patients. Fast-dissolving solid dispersions provide an ideal formulation in such cases. This report will provide an overview of current studies on fast-dissolving solid dispersions, including not only solid dispersion powders with fast dissolution rates but also specific does forms for the controlled release of poorly water-soluble drugs. Specifically, the applications of fast-dissolving solid dispersions will be described in every specific case. Moreover, pharmaceutical approaches and the utilization of polymers will be summarized. The classification and analysis of fast-dissolving solid dispersions could provide insight into strategies and potential applications in future drug delivery developments.

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.

Liquisolid Compacts Technique of Poor Water Soluble Drugs: An Overview

2021 ◽  
pp. 5569-5572
Author(s):  
E. Bhavya ◽  
M.D. Dhere
Keyword(s):  
Mathematical Models ◽  
Dissolution Rate ◽  
Coating Material ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Coating Materials ◽  
Poorly Water Soluble Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Liquisolid Compacts

Liquisolid technique is new and promising method that can use to enhance the dissolution rate of poorly water soluble drugs. Liquisolid compact technique is based upon the dissolving the drug in a suitable non-volatile solvent by using carrier and coating material for the conversion of acceptable flowing and compressible powders. By applying the mathematical models the carrier and coating materials optimized. In this case the drug is almost solubilised in the solvent or molecularly dispersed state which contributes the enhanced drug dissolution.

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