Phospholipid complex-loaded self-assembled phytosomal soft nanoparticles: evidence of enhanced solubility, dissolution rate, ex vivo permeability, oral bioavailability, and antioxidant potential of mangiferin

Background: The recent trend of herbal drug delivery has been focused on developing novel drug delivery carriers to address problems related to solubility, oral bioavailability, skin permeation and stability. The phyto-phospholipid complex (phytosomes®) technology has been used to overcome the problems associated with many conventional herbal extracts. Aim: The present work aimed to formulate phospholipid-complex of the flavanoid Hesperidin to enhance its dissolution leading to enhanced oral bioavailability. Method: The complex was prepared by refluxing various molar ratios of hesperidin and PC followed by solvent evaporation. The prepared complexes were evaluated for saturation solubility, partition co-efficient and drug content. The free drug and phospholipid complexes were analyzed in DSC. Surface morphology of the prepared complexes was viewed using SEM images. Selected formulations were subjected to in vitro drug release study. Antioxidant effect was examined by free radical scavenging method. Results: Solubility and partition coefficient of the prepared complexes were improved in comparison to free drug. Based on the results of solubility, partition coefficient and drug content, formulation F2 was selected as an optimized batch. DSC thermograms confirmed the formation of phospholipid complex. Free Hesperidin and Hesperidin-phospholipid complex (F2) showed 46.9 % and 78.20 % of drug release, respectively, at seven hours phosphate buffer (pH 7.4). The optimized formulation showed concentration-dependent anti-oxidant property. Conclusion: Results of the present study suggested that the phospholipid complex of Hesperidin possesses the antioxidant potential and may be of potential use for improving the dissolution of hesperidin and hence oral bioavailability.

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Freeze Dried Quetiapine-Nicotinamide Binary Solid Dispersions: A New Strategy for Improving Physicochemical Properties and Ex Vivo Diffusion

Journal of Pharmaceutics ◽

10.1155/2016/2126056 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Ahmed Mahmoud Abdelhaleem Ali ◽

Mayyas Mohammad Ahmad Al-Remawi

Keyword(s):

Physicochemical Properties ◽

Dissolution Rate ◽

Oral Bioavailability ◽

Ex Vivo ◽

Molar Ratio ◽

Scanning Calorimetry ◽

Intrinsic Dissolution ◽

Quetiapine Fumarate ◽

Intrinsic Dissolution Rate ◽

Freeze Dried

Improving the physicochemical properties and oral bioavailability of quetiapine fumarate (QF) enabling enhanced antipsychotic attributes are the main aims of this research. The freeze dried solid dispersion strategy was adopted using nicotinamide (NIC) as highly soluble coformer. The prepared dispersions were characterized using scanning electron microscopy (SEM) differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Static disc intrinsic dissolution rate and ex vivo diffusion through intestinal tissues were conducted and compared to pure quetiapine fumarate. The results demonstrated a highly soluble coamorphous system formed between quetiapine fumarate and nicotinamide at 1 : 3 molar ratio through H-bonding interactions. The results showed >14-fold increase in solubility of QF from the prepared dispersions. Increased intrinsic dissolution rate (from 0.28 to 0.603 mg cm−2 min−1) and faster flux rate through duodenum (from 0.027 to 0.041 mg cm−2 h−1) and jejunum (0.027 to 0.036 mg cm−2 h−1) were obtained. The prepared coamorphous dispersion proved to be effective in improving the drug solubility and dissolution rate and ex vivo diffusion. Therefore, binary coamorphous dispersions could be a promising solution to modify the physicochemical properties, raise oral bioavailability, and change the biopharmaceutics classification (BCS) of some active pharmaceutical ingredients.

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Development and Evaluation of Docetaxel-Phospholipid Complex Loaded Self-Microemulsifying Drug Delivery System: Optimization and In Vitro/Ex Vivo Studies

Pharmaceutics ◽

10.3390/pharmaceutics12060544 ◽

2020 ◽

Vol 12 (6) ◽

pp. 544

Author(s):

Miao Wang ◽

Sung-Kyun You ◽

Hong-Ki Lee ◽

Min-Gu Han ◽

Hyeon-Min Lee ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Anticancer Agents ◽

Lipid Membrane ◽

Ex Vivo ◽

System Optimization ◽

Raw Material ◽

Phospholipid Complex ◽

Low Solubility

Docetaxel (DTX) has clinical efficacy in the treatment of breast cancer, but it is difficult to develop a product for oral administration, due to low solubility and permeability. This study focused on preparing a self-microemulsifying drug delivery system (SME) loaded with DTX-phospholipid complex (DTX@PLC), to improve the dissolution and gastrointestinal (GI) permeability of DTX. A dual technique combining the phospholipid complexation and SME formulation described as improving upon the disadvantages of DTX has been proposed. We hypothesized that the complexation of DTX with phospholipids can improve the lipophilicity of DTX, thereby increasing the affinity of the drug to the cell lipid membrane, and simultaneously improving permeability through the GI barrier. Meanwhile, DTX@PLC-loaded SME (DTX@PLC-SME) increases the dissolution and surface area of DTX by forming a microemulsion in the intestinal fluid, providing sufficient opportunity for the drug to contact the GI membrane. First, we prepared DTX@PLC-SME by combining dual technologies, which are advantages for oral absorption. Next, we optimized DTX@PLC-SME with nanosized droplets (117.1 nm), low precipitation (8.9%), and high solubility (33.0 mg/g), which formed a homogeneous microemulsion in the aqueous phase. Dissolution and cellular uptake studies demonstrated that DTX@PLC-SME showed 5.6-fold higher dissolution and 2.3-fold higher DTX uptake in Caco-2 cells than raw material. In addition, an ex vivo gut sac study confirmed that DTX@PLC-SME improved GI permeability of DTX by 2.6-fold compared to raw material. These results suggested that DTX@PLC-SME can significantly overcome the disadvantages of anticancer agents, such as low solubility and permeability.

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Enhanced Solubility and Oral Bioavailability of Hydrophobic Drugs Using Pluronic Nanomicelles: An In‐Vitro Evaluation

ChemistrySelect ◽

10.1002/slct.202102123 ◽

2021 ◽

Vol 6 (28) ◽

pp. 7040-7048

Author(s):

Sofiya J. Shaikh ◽

Hemil S. Patel ◽

Debes Ray ◽

Vinod K. Aswal ◽

Sushmita Singh ◽

...

Keyword(s):

Oral Bioavailability ◽

Hydrophobic Drugs ◽

In Vitro Evaluation ◽

Enhanced Solubility

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Assessment of dissolution profile of Pantoprazole tablets available in Bangladesh

Stamford Journal of Pharmaceutical Sciences ◽

10.3329/sjps.v4i2.10441 ◽

2012 ◽

Vol 4 (2) ◽

pp. 58-62

Author(s):

Aparajita Malakar ◽

Bishwajit Bokshi ◽

Utpal Kumar Karmakar

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Water Soluble ◽

Dissolution Profile ◽

Coating Materials ◽

Volatile Solvents ◽

Kneading Method ◽

Enhanced Solubility ◽

Materials Used ◽

Liquisolid Compacts

The aim of the present study was to increase the solubility of a poorly water soluble BCS class II drug, valsartan. Liquisolid technology and solid dispersion by kneading method were techniques used to improve the solubility of the drug by using non-volatile solvents and some hydrophilic carriers. Liquisolid compacts were prepared by dissolving the drug in suitable non volatile solvents. The various non volatile solvents used were PG, PEG, and glycerine. The carrier coating materials play an important role in improving the solubility of the drug. The dissolution rate of the drug was increased by using propylene glycol as non-volatile solvent at 20:1 ratio of carrier to coating material. Solid dispersion by kneading method were another attempt to improve solubility the various carrier materials used were PVP K 30, PEG 6000 and mannitol, these carriers are used in various ratios to improve its solubility. The dissolution rate of drug using solid dispersion kneading method with mannitol was increased at 1:3 ratio. The DSC and FTIR studies revealed no drug excipients interactions, whereas XRD revealed the reduced crystalinity of drug, which showed enhanced solubility. From the results it was concluded that the liquisolid compacts enhanced the solubility of valsartan in comparison to traditional solid dispersion method.DOI: http://dx.doi.org/10.3329/sjps.v4i2.10441 S. J. Pharm. Sci. 4(2) 2011: 58-62

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PREPARATION AND CHARACTERIZATION OF NANOCRYSTALS FOR SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF PALIPERIDONE USING DIFFERENT HYDROPHILIC CARRIERS: IN VITRO-IN VIVO STUDY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i4.24964 ◽

2018 ◽

Vol 11 (4) ◽

pp. 393

Author(s):

Moon Rajkumar ◽

Gattani Surendra

Keyword(s):

Dissolution Rate ◽

Antipsychotic Agent ◽

Aqueous Solubility ◽

In Vivo Study ◽

Scanning Calorimetry ◽

Antisolvent Precipitation ◽

Enhanced Solubility ◽

Pure Drug

Objective: The objective of this study was to increase the solubility and dissolution rate of paliperidone (PAL) by preparing its nanocrystals using different hydrophilic carriers by antisolvent precipitation technique.Methods: The nanoparticles (NP) were characterized for aqueous solubility, drug content, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, particle size, and in vitro-in vivo analysis.Results: The results showed improved solubility and dissolution rate of NPs when compared to pure drug and physical mixture (PM). Solubility data showed a linear graph giving an indication that there is a gradual increase in the solubility profile of the drug with an increase in concentration of the carriers. At highest concentration, the solubility of NPs with Plasdone S630, Povidone K-25, and PVP K-30 found to be increased by 12 folds, 9 folds and 6 folds, respectively, as compared to pure drug. The release profile of NPs with Plasdone S630 in terms of dissolution efficiency at 60 min (DE60), initial dissolution rate (IDR), amount release in 15 min (Q15 min), and time for 75% release (t75%) shows better results when compared to pure drug, PM, and also NPs with povidone 25 and povidone 30. In vivo study reveals that optimized NPs elicited significant induction of cataleptic behavior which is the indication of antipsychotic agent(s) effect.Conclusion: The process antisolvent precipitation under constant stirring may be a promising method to produce stable PAL NPs with markedly enhanced solubility and dissolution rate due to nanonization with the increased surface area, improved wettability, and reduced diffusion pathway.

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