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

2020 ◽  
Vol 21 (7) ◽  
pp. 2506 ◽  
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.

scholarly journals Preparation and Characterization of PEG4000 Palmitate/PEG8000 Palmitate-Solid Dispersion Containing the Poorly Water-Soluble Drug Andrographolide

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Qingyun Zeng ◽  
Liquan Ou ◽  
Guowei Zhao ◽  
Ping Cai ◽  
Zhenggen Liao ◽  
...  
Keyword(s):  
Thermal Stability ◽  
Molecular Weight ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Water Solubility ◽  
Water Soluble ◽  
Carrier Material ◽  
Water Soluble Drug ◽  
Poorly Water Soluble ◽  
Poorly Water Soluble Drug

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.

scholarly journals ENHANCEMENT OF THE SOLUBILITY AND THE DISSOLUTION RATE OF TAMOXIFEN CITRATE SOLID DISPERSION USING SOLUPLUS BY SOLVENT EVAPORATION TECHNIQUE

2019 ◽  
Vol 12 (1) ◽  
pp. 216 ◽  
Author(s):  
Hayder Hussein Abduljabbar ◽  
Shaimaa Nazar Abd Alhammid
Keyword(s):  
Solid Dispersion ◽  
Water Solubility ◽  
Oral Absorption ◽  
Fourier Transforms ◽  
Amorphous State ◽  
Solvent Evaporation ◽  
Solubility Behavior ◽  
Tamoxifen Citrate ◽  
Complete Disintegration ◽  
Evaporation Technique

Objective: The aim of the present study was the enhancement in the solubility of tamoxifen citrate using solid dispersion which is considered as a great solution to overcome the poor water solubility behavior of tamoxifen citrate (TMX) by solvent evaporation technique using Soluplus® as a novel carrier then formulate it as an orodispersible tablet.Method: A total of 24 formulas were prepared as a solid dispersion by solvent evaporation method using Soluplus® as a polymeric solubilizer in the ratio of 1:1, 1:3, 1:5, 1:7, and 1:10 then formulated as orodispersible tablets by incorporating three types of superdisintegrants; croscarmellose, crospovidone, and sodium starch glycolate (SSG) with the solid dispersion. Characterization of the formulation was done using differential scanning colorimetry, Fourier transforms infrared spectroscopy, X-ray diffraction, and scanning electron microscope and the best formula was selected according to the disintegration and dissolution tests.Results and Discussion: Formula 22 were selected as the best formula which contains mixed types of superdisintegrants; croscarmellose and SSG with the fastest complete disintegration of 6.5 s and complete dissolution with <2 min.Conclusion: Accordingly, TMX was successfully enhanced its water solubility by converting its crystalline structure into the amorphous state through solid dispersion with Soluplus® and formulated as an orodispersible tablet to improve its oral absorption.

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

2016 ◽  
Vol 137 ◽  
pp. 350-359 ◽  
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

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

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

scholarly journals Evaluating the effect of the porous and non-porous colloidal silicon dioxide as a stabilizer on amorphous solid dispersion

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

Formulation Evaluation and Characterization of Fast Dissolving Tablets of Rofecoxib

2021 ◽  
pp. 60-64
Author(s):  
Preeti Mehra ◽  
Vishal Kapoor ◽  
Naveen Gupta ◽  
Dharmendra Singh Rajpoot ◽  
Neeraj Sharma
Keyword(s):  
Solid Dispersion ◽  
Water Solubility ◽  
Solid Dispersions ◽  
Amorphous State ◽  
Dissolution Profile ◽  
Major Drawback ◽  
Peg 4000 ◽  
Dissolution Efficiency ◽  
Pvp K30

Rofecoxib, a new non-steroidal anti-inflammatory agent mainly used for the treatment of osteoarthritis and rheumatoid arthritis. The major drawback of Rofecoxib is its very low water solubility, which results in poor bioavailability after oral administration. Hence, an attempt was made to formulate fast dissolving tablets of Rofecoxib. The solid dispersions of Rofecoxib were prepared with PEG-4000 and PVP K30 by solvent evaporation method. The characterization of prepared solid dispersions by FTIR, XRPD and DSC, which reveals lack of interaction with carriers and dictates amorphous state of solid dispersions. Solid dispersion of Rofecoxib with PVP K30 (1:6) showed maximum dissolution, therefore compressed into tablets by using microcrystalline cellulose, lactose and crosspovidone. The dissolution profile of developed fast dissolving tablets containing solid dispersion of Rofecoxib (1:6) was studied. The formulated formulations showed optimum dissolution efficiency.

scholarly journals Stable, Monodisperse, and Highly Cell-Permeating Nanocochleates from Natural Soy Lecithin Liposomes

Pharmaceutics ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 34 ◽  
Author(s):  
Martina Asprea ◽  
Francesca Tatini ◽  
Vieri Piazzini ◽  
Francesca Rossi ◽  
Maria Bergonzi ◽  
...  
Keyword(s):  
Calcium Ions ◽  
Room Temperature ◽  
Water Solubility ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Soy Lecithin ◽  
3T3 Fibroblasts ◽  
Therapeutic Value ◽  
Alkaline Conditions

(1) Background: Andrographolide (AN), the main diterpenoid constituent of Andrographis paniculata, has a wide spectrum of biological activities. The aim of this study was the development of nanocochleates (NCs) loaded with AN and based on phosphatidylserine (PS) or phosphatidylcholine (PC), cholesterol and calcium ions in order to overcome AN low water solubility, its instability under alkaline conditions and its rapid metabolism in the intestine. (2) Methods: The AN-loaded NCs (AN–NCs) were physically and chemically characterised. The in vitro gastrointestinal stability and biocompatibility of AN–NCs in J77A.1 macrophage and 3T3 fibroblasts cell lines were also investigated. Finally, the uptake of nanocarriers in macrophage cells was studied. (3) Results: AN–NCs obtained from PC nanoliposomes were suitable nanocarriers in terms of size and homogeneity. They had an extraordinary stability after lyophilisation without the use of lyoprotectants and after storage at room temperature. The encapsulation efficiency was 71%, while approximately 95% of AN was released in PBS after 24 h, with kinetics according to the Hixson–Crowell model. The in vitro gastrointestinal stability and safety of NCs, both in macrophages and 3T3 fibroblasts, were also assessed. Additionally, NCs had extraordinary uptake properties in macrophages. (4) Conclusions: NCs developed in this study could be suitable for both AN oral and parental administration, amplifying its therapeutic value.

scholarly journals Hot-Melt Extruded Amorphous Solid Dispersion for Solubility, Stability, and Bioavailability Enhancement of Telmisartan

2021 ◽  
Vol 14 (1) ◽  
pp. 73
Author(s):  
Bhupendra Raj Giri ◽  
Jaewook Kwon ◽  
Anh Q. Vo ◽  
Ajinkya M. Bhagurkar ◽  
Suresh Bandari ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous State ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Hydrophilic Polymer ◽  
Dissolution Profile ◽  
Maximum Serum ◽  
Hot Melt

Telmisartan (TEL, an antihypertensive drug) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its poor aqueous solubility. In this study, we enhanced the solubility, bioavailability, and stability of TEL through the fabrication of TEL-loaded pH-modulated solid dispersion (TEL pHM-SD) using hot-melt extrusion (HME) technology. We prepared different TEL pHM-SD formulations by varying the ratio of the drug (TEL, 10–60% w/w), the hydrophilic polymer (Soluplus®, 30–90% w/w), and pH-modifier (sodium carbonate, 0–10% w/w). More so, the tablets prepared from an optimized formulation (F8) showed a strikingly improved in vitro dissolution profile (~30-fold) compared to the free drug tablets. The conversion of crystalline TEL to its amorphous state is observed through solid-state characterizations. During the stability study, F8 tablets had a better stability profile compared to the commercial product with F8, showing higher drug content, low moisture content, and negligible physical changes. Moreover, compared to the TEL powder, in vivo pharmacokinetic studies in rats showed superior pharmacokinetic parameters, with maximum serum concentration (Cmax) and area under the drug concentration–time curve (AUC0–∞) of the TEL pHM-SD formulation increasing by 6.61- and 5.37-fold, respectively. Collectively, the results from the current study showed that the inclusion of a hydrophilic polymer, pH modulator, and the amorphization of crystalline drugs in solid dispersion prepared by HME can be an effective strategy to improve the solubility and bioavailability of hydrophobic drugs without compromising the drug’s physical stability.

Mechanochemical preparation of chrysomycin A self-micelle solid dispersion with improved solubility and enhanced oral bioavailability

2021 ◽  
Author(s):  
Zhuomin Xu ◽  
Shanshan Zheng ◽  
Yulu Hong ◽  
Yue Cai ◽  
Qiuqin Zhang ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Biological Activities ◽  
Low Cost ◽  
Polarized Light ◽  
Average Diameter ◽  
Future Application ◽  
Amorphous Solid Dispersion ◽  
Self Assembled

Abstract Background: Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (Na2GA) as an excipient, an amorphous solid dispersion (Na2GA/CA-BM) consisting of CA and Na2GA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, Na2GA/CA-BM was self-assembled to micelles in water. The interaction of CA and Na2GA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of Na2GA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy.Results: CA encapsulated by Na2GA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was -11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about 2 time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that Na2GA/CA-BM had an excellent inhibition of tumor growth.Conclusions: Na2GA/CA-BM nanoparticles (131.6 nm, -11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment.

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