Highly Water-Soluble Solid Dispersions of Honokiol: Preparation, Solubility, and Bioavailability Studies and Anti-Tumor Activity Evaluation

Honokiol (HK), a well-tolerated natural product, has many multiple pharmacological activities. However, its poor water solubility and low bioavailability limit its clinical application and development. The aim of this research was to prepare the solid dispersion (SD) formulation of honokiol (HK) with poloxamer-188 (PLX) as the carrier, thereby improving its solubility and oral bioavailability. Firstly, by investigating the relationship between the addition amount of the PLX and the solubility of HK, and the effects of solid dispersions with different ratios of HK–PLX on the solubility of HK, we determined that the optimum ratio of PLX to HK was (1:4). Then, the HK–PLX (1:4) SD of HK was prepared using the solvent evaporation method. The morphology of the obtained HK–PLX (1:4) SD was different from that of free HK. The HK in the HK–PLX (1:4) SD existed in amorphous form and formed intermolecular hydrogen bonds with PLX. Additionally, the solubility values of the HK–PLX (1:4) SD were about 32.43 ± 0.36 mg/mL and 34.41 ± 0.38 mg/mL in artificial gastric juice (AGJ) and in artificial intestinal juice (AIJ), respectively. Compared with free HK, the release rate and the bioavailability was also substantially improved for HK in its SD form. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the HK–PLX (1:4) SD showed higher inhibition of HepG2 cells than free HK. Taken together, the present study suggests that the HK–PLX (1:4) SD could become a new oral drug formulation with high bioavailability and could produce a better response for clinical applications of HK.

Download Full-text

Enhanced Water Solubility and Oral Bioavailability of Paclitaxel Crystal Powders through an Innovative Antisolvent Precipitation Process: Antisolvent Crystallization Using Ionic Liquids as Solvent

Pharmaceutics ◽

10.3390/pharmaceutics12111008 ◽

2020 ◽

Vol 12 (11) ◽

pp. 1008 ◽

Cited By ~ 1

Author(s):

Qilei Yang ◽

Chang Zu ◽

Wengang Li ◽

Weiwei Wu ◽

Yunlong Ge ◽

...

Keyword(s):

Oral Bioavailability ◽

High Performance ◽

Water Solubility ◽

Water Soluble ◽

Precipitation Process ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Antisolvent Precipitation ◽

Antisolvent Crystallization ◽

Artificial Gastric Juice

Paclitaxel (PTX) is a poor water-soluble antineoplastic drug with significant antitumor activity. However, its low bioavailability is a major obstacle for its biomedical applications. Thus, this experiment is designed to prepare PTX crystal powders through an antisolvent precipitation process using 1-hexyl-3-methylimidazolium bromide (HMImBr) as solvent and water as an antisolvent. The factors influencing saturation solubility of PTX crystal powders in water in water were optimized using a single-factor design. The optimum conditions for the antisolvent precipitation process were as follows: 50 mg/mL concentration of the PTX solution, 25 °C temperature, and 1:7 solvent-to-antisolvent ratio. The PTX crystal powders were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, high-performance liquid chromatography–mass spectrometry, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Raman spectroscopy, solid-state nuclear magnetic resonance, and dissolution and oral bioavailability studies. Results showed that the chemical structure of PTX crystal powders were unchanged; however, precipitation of the crystalline structure changed. The dissolution test showed that the dissolution rate and solubility of PTX crystal powders were nearly 3.21-folds higher compared to raw PTX in water, and 1.27 times higher in artificial gastric juice. Meanwhile, the bioavailability of PTX crystal increased 10.88 times than raw PTX. These results suggested that PTX crystal powders might have potential value to become a new oral PTX formulation with high bioavailability.

Download Full-text

Albendazole solid dispersions against alveolar echinococcosis: a pharmacotechnical strategy to improve the efficacy of the drug

Parasitology ◽

10.1017/s0031182020000670 ◽

2020 ◽

Vol 147 (9) ◽

pp. 1026-1031

Author(s):

Julia Fabbri ◽

Patricia Eugenia Pensel ◽

Clara María Albani ◽

Lurdes Milagros Lopez ◽

Analia Simonazzi ◽

...

Keyword(s):

Alveolar Echinococcosis ◽

Water Solubility ◽

Solid Dispersions ◽

Water Soluble ◽

Poloxamer 407 ◽

Infection Model ◽

Efficacy Study ◽

Dissolution Profile ◽

Germinal Layer

AbstractAlveolar echinococcosis is a neglected parasitic zoonosis caused by Echinococcus multilocularis. The pharmacological treatment is based on albendazole (ABZ). However, the low water solubility of the drug produces a limited dissolution rate, with the consequent failure in the treatment of the disease. Solid dispersions are a successful pharmacotechnical strategy to improve the dissolution profile of poorly water-soluble drugs. The aim of this work was to determine the in vivo efficacy of ABZ solid dispersions using poloxamer 407 as a carrier (ABZ:P407 solid dispersions (SDs)) in the murine intraperitoneal infection model for secondary alveolar echinococcosis. In the chemoprophylactic efficacy study, the ABZ suspension, the ABZ:P407 SDs and the physical mixture of ABZ and poloxamer 407 showed a tendency to decrease the development of murine cysts, causing damage to the germinal layer. In the clinical efficacy study, the ABZ:P407 SDs produced a significant decrease in the weight of murine cysts. In addition, the SDs produced extensive damage to the germinal layer. The increase in the efficacy of ABZ could be due to the improvement of water solubility and wettability of the drug due to the surfactant nature of poloxamer 407. In conclusion, this study is the basis for further research. This pharmacotechnical strategy might in the future offer novel treatment alternatives for human alveolar echinococcosis.

Download Full-text

SPRAY DRYING APPROACH IN PREPARATION AND CHARACTERIZATION OF SOLID DISPERSION OF EPROSARTAN MESYLATE

Journal of medical pharmaceutical and allied sciences ◽

10.22270/jmpas.v10i3.1226 ◽

2021 ◽

Vol 10 (3) ◽

pp. 2929-2932

Author(s):

Sachin N Kothawade

Keyword(s):

Spray Drying ◽

Solid Dispersion ◽

Water Solubility ◽

Solid Dispersions ◽

Weight Ratio ◽

Water Soluble ◽

Drying Methods ◽

Scanning Calorimetry ◽

Dispersion Systems ◽

Physicochemical Features

Spray drying methods were used to make solid dispersions of the medication Eprosartan Mesylate, which is poorly water-soluble. X-ray Powder diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry were used to characterize the products' physicochemical features as well as drug-polymer interactions. Eprosartan Mesylate was shown to be dispersed amorphously in both solid dispersion systems, with a drug to polymer weight ratio of 1:4.The drug and polymer created hydrogen bonds, according to the spectrum data. Both techniques utilized in this investigation enhanced Eprosartan Mesylate solubility. Solid dispersions, on the other hand, performed significantly better, dissolving completely in 5 minutes and at a rate that was about 20 times faster than API within the first 15 minutes. Spray drying is a good way to boost the bioavailability of drugs that are poor water solubility.

Download Full-text

Increasing Solubility of Poorly Water Soluble Drug Resveratrol by Surfactants and Cyclodextrins

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.418-420.2231 ◽

2011 ◽

Vol 418-420 ◽

pp. 2231-2234 ◽

Cited By ~ 7

Author(s):

Mont Kumpugdee-Vollrath ◽

Yvonne Ibold

Keyword(s):

Solid Dispersion ◽

Water Solubility ◽

Solid Dispersions ◽

Water Soluble ◽

Dispersion Phase ◽

Water Soluble Drug ◽

Vis Spectroscopy ◽

Anti Cancer ◽

Cancer Agent ◽

Span 60

Resveratrol (Res) is a polyphenolic secondary natural substance and can be used as anti-inflammatory, anti-aging, anti-heart disease and anti-cancer agent. However, Res has low water solubility which causes a low bioavailability in human body. In order to increase solubility we have prepared different inclusion complexes with native ((α, β, γ) and modified (2-hydroxypropyl-beta, dimethyl-beta) cyclodextrins (Cd) as well as solid dispersions using several surfactants (Imwitor 742, Imwitor 928, PEG 6000, Span 40, Span 60, Solutol HS15) with Res. The solubility of all mixtures was determined by UV-VIS spectroscopy at the wavelength of 305 nm. Regarding the Cd, the complex of Res with 2-hydroxypropyl-beta-Cd at a ratio of 1:3 showed the highest water solubility (248210 g/l). Concerning the surfactants, the solid dispersion from Res and Solutol HS15 showed the highest water solubility (16140 g/l). The complexation and the solid dispersion phase were confirmed by DSC. The results will be a basis for better formulation of resveratrol with higher bioavailability.

Download Full-text

SOLUBILITY ENHANCEMENT OF POOR WATER SOLUBLE DRUGS BY SOLID DISPERSION: A REVIEW

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v8i5.1887 ◽

2018 ◽

Vol 8 (5) ◽

pp. 44-49 ◽

Cited By ~ 1

Author(s):

SD Mankar ◽

Punit R. Rach

Keyword(s):

Solid Dispersion ◽

High Throughput Screening ◽

Water Solubility ◽

Solid Dispersions ◽

Scale Up ◽

Solubility Enhancement ◽

Water Soluble ◽

Formulation Development ◽

Solubility Behavior ◽

Poorly Water Soluble

The solubility behavior of drugs remains one of the most exigent aspects in formulation development. With the advent of combinatorial chemistry and high throughput screening, the number of poorly water soluble compounds has dramatically increased. Among all the newly discovered chemical entities, about 40-45% drugs fail to reach market due to their poor water solubility. Because of solubility problem, bioavailability of drugs gets affected and hence solubility enhancement becomes necessary. Solid dispersions have attracted considerable interest as an efficient means of improving the dissolution rate and hence the bioavailability of drugs. Therefore, the application of this technique proves to be an important stratagem for pharmaceutical companies. However, the in - depth knowledge of the solid dispersion is desired for the scale up of formulation, from laboratory scale to industrial scale. There are various methods available to improve the solubility of the new drug in which solid dispersion emerged promising. A Solid dispersion generally composed of two components- the drug and the polymer matrix. Hence, this approach is expected to form a basis for the commercialization of many poorly water-soluble and water-insoluble drugs in their solid-dispersion formulations in the near future. This article reviews the various preparation techniques, carriers used, advantages and limitations of solid dispersions and compiles some of the recent advances. Keywords: Bioavailability, Solid Dispersion, Hydrophilic carriers, Polyethylene glycol.

Download Full-text

A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery

Pharmaceutics ◽

10.3390/pharmaceutics11120625 ◽

2019 ◽

Vol 11 (12) ◽

pp. 625 ◽

Cited By ~ 1

Author(s):

Georgia Tsakiridou ◽

Christos Reppas ◽

Martin Kuentz ◽

Lida Kalantzi

Keyword(s):

In Silico ◽

Oral Drug Delivery ◽

Solid Dispersions ◽

Amorphous Solid ◽

Water Soluble ◽

Oral Drug ◽

Main Task ◽

Formulation Development ◽

Scanning Calorimetry ◽

Polymer Interactions

Solid dispersions provide a key technology to formulate poorly water-soluble drugs, and a main task of early development is appropriate selection of polymer. This study investigates the use of a novel rheology-based approach to evaluate miscibility and interactions of drugs with polymers regarding amorphous solid drug dispersions for oral administration. Tacrolimus was used as model drug and hydroxypropyl cellulose, ethylcellulose, Soluplus®, polyethyleneglycol 6000, Poloxamer-188 (Koliphor-188), and Eudragit® S100 were used as excipients. Solvent-based evaporation methods were used to prepare binary solid dispersions of drug and polymer. Data of the dilute solution viscosimetry were compared with in silico calculations of the Hansen solubility parameter (HSP), as well as phase separation/crystallization data obtained from X-ray diffraction and differential scanning calorimetry. HSP calculations in some cases led to false positive predictions of tacrolimus miscibility with the tested polymers. The novel rheology-based method provided valuable insights into drug-polymer interactions and likely miscibility with polymer. It is a rather fast, inexpensive, and robust analytical approach, which could be used complementary to in silico-based evaluation of polymers in early formulation development, especially in cases of rather large active pharmaceutical ingredients.

Download Full-text

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

Current Pharmaceutical Design ◽

10.2174/1381612826666201021125844 ◽

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.

Download Full-text

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

Molecules ◽

10.3390/molecules24193471 ◽

2019 ◽

Vol 24 (19) ◽

pp. 3471 ◽

Cited By ~ 8

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.

Download Full-text

Engineering of Nanofibrous Amorphous and Crystalline Solid Dispersions for Oral Drug Delivery

Pharmaceutics ◽

10.3390/pharmaceutics11010007 ◽

2018 ◽

Vol 11 (1) ◽

pp. 7 ◽

Cited By ~ 8

Author(s):

Laura Modica de Mohac ◽

Alison Keating ◽

Maria de Fátima Pina ◽

Bahijja Raimi-Abraham

Keyword(s):

Oral Drug Delivery ◽

Solid Dispersions ◽

Aqueous Solubility ◽

Water Soluble ◽

Oral Drug ◽

Crystalline Solid ◽

Particle Size Reduction ◽

Emerging Trends ◽

Nano Crystalline ◽

Water Soluble Drugs

Poor aqueous solubility (<0.1 mg/mL) affects a significant number of drugs currently on the market or under development. Several formulation strategies including salt formation, particle size reduction, and solid dispersion approaches have been employed with varied success. In this review, we focus primarily on the emerging trends in the generation of amorphous and micro/nano-crystalline solid dispersions using electrospinning to improve the dissolution rate and in turn the bioavailability of poorly water-soluble drugs. Electrospinning is a simple but versatile process that utilizes electrostatic forces to generate polymeric fibers and has been used for over 100 years to generate synthetic fibers. We discuss the various electrospinning studies and spinneret types that have been used to generate amorphous and crystalline solid dispersions.

Download Full-text

Nanocrystalization: An Emerging Technology to Enhance the Bioavailability of Poorly Soluble Drugs

Pharmaceutical Nanotechnology ◽

10.2174/2211738507666190405182524 ◽

2019 ◽

Vol 7 (4) ◽

pp. 259-278 ◽

Cited By ~ 2

Author(s):

Kavita Joshi ◽

Akhilesh Chandra ◽

Keerti Jain ◽

Sushama Talegaonkar

Keyword(s):

Water Solubility ◽

Drug Loading ◽

Chemical Properties ◽

Active Pharmaceutical Ingredient ◽

Pharmaceutical Product ◽

Drug Formulation ◽

Water Soluble ◽

Drug Candidate ◽

Formulation Development ◽

New Formulation

Most of the active pharmaceutical ingredient used in the management of disease have poor water solubility and offer grueling problems in drug formulation development since low solubility is generally associated with poor dissolution characteristics which leads to poor oral bioavailability. The great challenge for the development of a pharmaceutical product is to create its new formulation and drug delivery system to limit solubility problems of existing drug candidate. Limited drug-loading capacity requires a large amount of carrier material to get appropriate encapsulation of the drug, which is another major challenge in the development of pharmaceutical product which could be resolved by developing nanocrystals (NCs). A significant research in the past few years has been done to develop NCs which helps in the delivery of poorly water soluble drugs via different routes. The technology could continue to thrive as a useful tool in pharmaceutical sciences for the improvement of drug solubility, absorption and bioavailability. Many crystalline compounds have pulled in incredible consideration much of the time, due to their ability to show good physical and chemical properties when contrasted with their amorphous counterparts. Nanocrystals have been proven to show atypical properties compared to the bulk. This review article explores the principles of the important nanocrystallization techniques including NCs characterization and its application.

Download Full-text