Effect of poloxamer on physicochemical properties of tacrolimus solid dispersion improving water solubility and dissolution rate

Solid dispersion (SD) is the effective approach to improve the dissolution rate and bioavailability of class II drugs with low water solubility and high tissue permeability in the Biopharmaceutics Classification System. This study investigated the effects of polyethylene glycol (PEG) molecular weight in carrier material PEG palmitate on the properties of andrographolide (AG)-SD. We prepared SDs containing the poorly water-soluble drug AG by the freeze-drying method. The SDs were manufactured from two different polymers, PEG4000 palmitate and PEG8000 palmitate. The physicochemical properties of the AG-SDs were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, dissolution testing, and so on. We found that AG-PEG4000 palmitate-SD and AG-PEG8000 palmitate-SD were similar in the surface morphology, specific surface area, and pore volume. Compared with the AG-PEG4000 palmitate-SD, the intermolecular interaction between PEG8000 palmitate and AG was stronger, and the thermal stability of AG-PEG8000 palmitate-SD was better. In the meanwhile, the AG relative crystallinity was lower and the AG dissolution rate was faster in AG-PEG8000 palmitate-SD. The results demonstrate that the increasing PEG molecular weight in the PEG palmitate can improve the compatibility between the poorly water-soluble drug and carrier material, which is beneficial to improve the SD thermal stability and increases the dissolution rate of poorly water-soluble drug in the SD.

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Oral Bioavailability Enhancement and Anti-Fatigue Assessment of the Andrographolide Loaded Solid Dispersion

International Journal of Molecular Sciences ◽

10.3390/ijms21072506 ◽

2020 ◽

Vol 21 (7) ◽

pp. 2506 ◽

Cited By ~ 1

Author(s):

Ching-Chi Yen ◽

Yu-Kai Liang ◽

Chao-Pei Cheng ◽

Mei-Chich Hsu ◽

Yu-Tse Wu

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Oral Bioavailability ◽

Water Solubility ◽

Biological Activities ◽

Wide Spectrum ◽

Amorphous State ◽

Vehicle Group ◽

Time To Exhaustion ◽

Pharmacokinetic Studies

Andrographolide (AG), a major diterpene lactone isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae), possesses a wide spectrum of biological activities. However, its poor water solubility and low bioavailability limit its clinical application. Therefore, this study aimed to develop a solid dispersion (SD) formulation to increase the aqueous solubility and dissolution rate of AG. Different drug-polymer ratios were used to prepare various SDs. The optimized formulation was characterized for differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffraction. The analysis indicated that the optimized SD enhanced AG solubility and dissolution rates by changing AG crystallinity to an amorphous state. The dissolution behaviors of the optimum SD composed of an AG-polyvinylpyrrolidone K30-Kolliphor EL ratio of 1:7:1 (w/w/w) resulted in the highest accumulated dissolution (approximately 80%). Pharmacokinetic studies revealed that Cmax/dose and the AUC/dose increased by 3.7-fold and 3.0-fold, respectively, compared with AG suspension. Furthermore, pretreatment using the optimized AG-SD significantly increased the swimming time to exhaustion by 1.7-fold and decreased the plasma ammonia level by 71.5%, compared with the vehicle group. In conclusion, the optimized AG-SD formulation appeared to effectively improve its dissolution rate and oral bioavailability. Moreover, the optimized AG-SD provides a promising treatment against physical fatigue.

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Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs

Carbohydrate Polymers ◽

10.1016/j.carbpol.2015.10.070 ◽

2016 ◽

Vol 137 ◽

pp. 350-359 ◽

Cited By ~ 35

Author(s):

Paola Aline Amarante Borba ◽

Marihá Pinotti ◽

Carlos Eduardo Maduro de Campos ◽

Bianca Ramos Pezzini ◽

Hellen Karine Stulzer

Keyword(s):

Dissolution Rate ◽

Sodium Alginate ◽

Solid Dispersion ◽

Water Solubility

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Formulation and In-Vitro Evaluation of Meloxicam Solid Dispersion using Natural Polymers.

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol30iss1pp169-178 ◽

2021 ◽

Vol 30 (1) ◽

pp. 169-178

Author(s):

Hiba Radhi ALhassani ◽

Eman B. H. Al-Khedairy

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Water Solubility ◽

Oral Absorption ◽

Chemical Interaction ◽

Water Soluble ◽

Natural Polymers ◽

Drug Content ◽

Percentage Yield

Meloxicam (MLX) is non-steroidal anti -inflammatory, poorly water soluble, highly permeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Solid dispersion (SD) is an effective technique for enhancing the solubility and dissolution rate of such drug. The present study aims to enhance the solubility and the dissolution rate of MLX by SD technique by solvent evaporation method using sodium alginate (SA), hyaluronic acid (HA), collagen and xyloglucan (XG) as gastro-protective hydrophilic natural polymers. Twelve formulas were prepared in different drug: polymer ratios and evaluated for their, percentage yield, drug content, water solubility, dissolution, crystal lattice using powder X-ray diffraction (PXRD) and studies and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug-polymer interaction. All the prepared showed improvement of drug solubility except that prepared with HA. The best result was obtained with formula SD1 (MLX: SA 1:1) that showed a high percentage yield (97), high drug content (97.4±0.05) and increase in solubility compared to solubility of pure MLX with improved dissolution rate. the PXRD study revealed the conversion of the drug to amorphous form without chemical interaction according to FTIR results

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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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Tedizolid-Cyclodextrin System as Delayed-Release Drug Delivery with Antibacterial Activity

International Journal of Molecular Sciences ◽

10.3390/ijms22010115 ◽

2020 ◽

Vol 22 (1) ◽

pp. 115

Author(s):

Magdalena Paczkowska-Walendowska ◽

Natalia Rosiak ◽

Ewa Tykarska ◽

Katarzyna Michalska ◽

Anita Płazińska ◽

...

Keyword(s):

Drug Delivery ◽

Physicochemical Properties ◽

Dissolution Rate ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Water Solubility ◽

Solid Dispersions ◽

Biological Properties ◽

Thermal Method ◽

Microbiological Activity

Progressive increase in bacterial resistance has caused an urgent need to introduce new antibiotics, one of them being oxazolidinones with their representative tedizolid. Despite the broad spectrum of activity of the parent tedizolid, it is characterized by low water solubility, which limits its use. The combination of the active molecule with a multifunctional excipient, which is cyclodextrins, allows preservation of its pharmacological activity and modification of its physicochemical properties. Therefore, the aim of the study was to change the dissolution rate and permeability through the model membrane of tedizolid by formation of solid dispersions with a cyclodextrin. The research included identification of tedizolid-hydroxypropyl-β-cyclodextrin (tedizolid/HP-β-CD) inclusion complex by thermal method (Differential Scanning Colorimetry), spectroscopic methods (powder X-ray diffraction, Fourier-Transform Infrared spectroscopy), and molecular docking. The second part of the research concerned the physicochemical properties (dissolution and permeability) and the biological properties of the system in terms of its microbiological activity. An increase in the dissolution rate was observed in the presence of cyclodextrin, while maintaining a high permeation coefficient and high microbiological activity. The proposed approach is an opportunity to develop drug delivery systems used in the treatment of resistant bacterial infections, in which, in addition to modifying the physicochemical properties caused by cyclodextrin, we observe a favorable change in the pharmacological potential of the bioactives.

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FORMULATION AND EVALUATION OF TELMISARTAN SOLID DISPERSIONS USING ENTADA SCANDENS SEED STARCH AND POLOXAMER-188 AS SUPERDISINTEGRANTS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i9.28422 ◽

2018 ◽

Vol 11 (9) ◽

pp. 474

Author(s):

Venkatarao Mannem ◽

Vidyadhara Suryadevara ◽

Sandeep Doppalapudi

Keyword(s):

Physicochemical Properties ◽

Sodium Hydroxide ◽

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Water Soluble ◽

In Vitro Dissolution ◽

Differential Scanning Calorimetric ◽

Poloxamer 188

Objective: The current research focuses on solubility enhancement of poorly water-soluble drug telmisartan, using novel superdisintegrants such as Entada scandens seed starch and Poloxamer-188. Starches yielded from plants are pharmaceutically useful as binders, diluents, disintegrants, and lubricants.Methods: Starches were extracted from E. scandens seed powder using alkali method (sodium hydroxide at 0.1%, 0.25%, and 0.5% concentrations) and water. These starches were subjected for the evaluation of various physicochemical properties and phytochemical tests.Results: The phytochemical tests revealed the presence of only starch in all the extracts. Of all the starches, the starch prepared from 0.5% sodium hydroxide (ESS4) showed best physicochemical properties. Solid dispersions were prepared using telmisartan, poloxamer-188, and starch (ESS4) in various concentrations using fusion technique. Various pre-formulation parameters were evaluated. From in vitro dissolution studies, it was observed that the solid dispersion formulation TP7 containing telmisartan and poloxamer-188 in 1:4 ratios showed better dissolution rate. Solid dispersion TPS7 containing TP7 formulation and 15% w/w of alkali extracted starch showed faster disintegration and enhanced dissolution rate than the solid dispersions prepared alone with poloxamer-188. Fourier transform infrared spectroscopy and differential scanning calorimetric studies for optimized formulations revealed that there were no major interactions between the drug and excipients. X-ray diffraction studies revealed the crystalline and amorphous nature of formulations.Conclusion: Thus, the solid dispersions prepared using E. scandens seed starch revealed the superdisintegrant property of starch.

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Solubility and Dissolution Enhancement of Ebastine by Surface Solid Dispersion Technique

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol30iss1pp122-132 ◽

2021 ◽

Vol 30 (1) ◽

pp. 122-132

Author(s):

Lna S. Hussein ◽

Eman B. H. Al-Khedairy

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Water Solubility ◽

Chemical Interaction ◽

Drug Carrier ◽

Dissolution Enhancement ◽

Duration Of Action ◽

Drug Content ◽

Percentage Yield ◽

Dispersion Technique

Ebastine (EBS) is a non-sedating antihistamine with a long duration of action. This drug has predominantly hydrophobic property causing a low solubility and low bioavailability. Surface solid dispersions (SSD) is an effective technique for improving the solubility and dissolution rate of poorly soluble drugs by using hydrophilic water insoluble carriers. The present study aims to enhance the solubility and dissolution rate of EBS by using surface solid dispersion technique. Avicel® PH101, Avicel® PH 102, croscarmellose sodium(CCS) and sodium starch glycolate(SSG) were used as water insoluble hydrophilic carriers. The SSD formulations of EBS were prepared by the solvent evaporation method in different drug: carrier weight ratios and evaluated for their percentage yield, drug content , water solubility, dissolution study in 0.1 N HCl, crystal lattice using powder X-ray diffraction (PXRD) and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug-carrier interaction. Most of the prepared SSD formulas showed improvement of drug solubility. The best result was obtained with formula SSD16 (EBS:CCS 1:15) that showed high percentage yield (98.5%), high drug content (98.39%) and 8.2 fold increase in solubility compared to solubility of pure drug with improved dissolution rate. The drug was converted to amorphous form without chemical interaction with the carrier.

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Formulation Design and Optimization of Repaglinide Solid Dispersions by Central Composite Design

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.6.7 ◽

2018 ◽

Vol 11 (6) ◽

pp. 4337-4348

Author(s):

Bhikshapathi D. V. R. N. ◽

Srinivas I

Keyword(s):

Central Composite Design ◽

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Solvent Evaporation ◽

Release Mechanism ◽

Solvent Evaporation Method ◽

Onset Of Action ◽

Evaporation Method ◽

Central Composite

Repaglinide is a pharmaceutical drug used for the treatment of type II diabetes mellitus, it is characterized with poor solubility which limits its absorption and dissolution rate and delays onset of action. In the present study, immediate release solid dispersion of repaglinide was formulated by solvent evaporation technique. Repaglinide solid dispersions were prepared using PEG 8000, Pluronic F 127 and Gelucire 44/14 by solvent evaporation method. A 3-factor, 3-level central composite design employed to study the effect of each independent variable on dependent variables. FTIR studies revealed that no drug excipient interaction takes place. From powder X-ray diffraction (p-XRD) and by scanning electron microscopy (SEM) studies it was evident that polymorphic form of repaglinide has been converted into an amorphous form from crystalline within the solid dispersion formulation. The correlation coefficient showed that the release profile followed Higuchi model anomalous behavior and hence release mechanism was indicative of diffusion. The obtained results suggested that developed solid dispersion by solvent evaporation method might be an efficacious approach for enhancing the solubility and dissolution rate of repaglinide.

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New Technological Approach for Glycyrrethic Acid Oral and Topical Administration

Current Pharmaceutical Design ◽

10.2174/1381612826666191226112249 ◽

2020 ◽

Vol 26 (6) ◽

pp. 664-674 ◽

Cited By ~ 2

Author(s):

Cinzia Pagano ◽

Luana Perioli ◽

Paola Calarco ◽

Alessandro Di Michele ◽

Maria C. Tiralti ◽

...

Keyword(s):

Dissolution Rate ◽

Water Solubility ◽

Local Therapy ◽

Topical Administration ◽

Application Site ◽

Vaginal Mucosa ◽

Anionic Clays ◽

Dissolution Rate Enhancement ◽

Technological Approach ◽

Bioactive Component

Background: 18β- glycyrrhetinic acid (Gly) is the major bioactive component of licorice roots and rhizomes of the Glycyrrhiza glabra species. It shows many activities such as antiviral, anti-inflammatory, antioxidant, antimicrobial, and antifungal, however, its use in the health field is very limited due to the low water solubility. Methods: This paper deals with the development of a new technological approach for Gly dissolution rate enhancement. It consists of Gly intercalation (guest) in the interlamellar spaces between the inorganic spaces (host) of the anionic clays “hydrotalcites” (HTlc) to obtain hybrids MgAl-HTlc-Gly and ZnAl-HTlc-Gly. Gly can find applications in both systemic and local therapies, thus advantages of the use of the hybrids in these two fields were investigated. Results: Gly dissolution rate from hybrids in the intestinal environment, site in which it is preferentially absorbed, resulted enhanced (ZnAl-HTlc-Gly > MgAl-HTlc-Gly) compared to the crystalline form, thereby, making them suitable for oral administration as dry powder in hard capsules. : For a local therapy, bioadhesive, vaginal emulgels loaded with the hybrids were developed. These showed suitable mucoadhesive property to the vaginal mucosa, necessary to prolong the residence time in the application site. The emulgel containing ZnAl-HTlc-Gly showed a faster and higher release profile than that containing MgAl- HTlc-Gly. Conclusions: The obtained results suggest that Gly intercalation into HTlc, especially in ZnAl-HTlc, allows to enhance Gly dissolution when the hybrids are formulated both as oral or topical products.

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