scholarly journals Cocrystals of Modafinil-Nicotinic Acid: A Novel Cocrystal for Enhanced Bioavailability

Proceedings ◽  
2021 ◽  
Vol 62 (1) ◽  
pp. 12
Author(s):  
Tanmoy Ghosh ◽  
Thimmasetty Juturu ◽  
Shashank Nayak Nagar ◽  
Shwetha Kamath
Keyword(s):  
Nicotinic Acid ◽  
Crystal Engineering ◽  
Methyl Cellulose ◽  
Aqueous Solubility ◽  
Potential Method ◽  
Molar Ratio ◽  
Scanning Calorimetry ◽  
Bioavailability Enhancement ◽  
Precipitation Inhibitor

In this work, we are the first to identify and report pharmaceutically effective cocrystals of the poorly soluble drug Modafinil (MOD) using a crystal engineering approach. A multi-component system of MOD with nicotinic acid (NIC) as the coformer at a 1:1 molar ratio was prepared to simultaneously improve the solubility, dissolution and bioavailability by applying a liquid assistant grinding technique. Nicotinic acid as a potential coformer for cocrystal preparation was predicted using a novel approach of the Hansen Solubility Parameter (HSP) group contribution method. Various evaluation parameters pertaining to confirm cocrystal formation, such as Fourier transformer infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and field emission scanning electron microscopy (FESEM) were carried out. Further effects of precipitation inhibitor Hydroxypropyl methyl cellulose (HPMC) on in-vivo bioavailability enhancement were also studied. MOD-NIC cocrystals formation was confirmed by integrating the results of instrumental techniques. Aqueous solubility and in-vivo pharmacokinetic study proved 5.96 and 1.88 times higher bioavailability, respectively, in the case of prepared cocrystals compared to MOD alone, whereas bioavailability further increased by 2.72 times when these cocrystals were administered in the presence of precipitation inhibitor. Hence, solid state manipulation was successful for preparing modafinil cocrystals as a potential method for illustrating several properties. The concept of cocrystals coupled with precipitation inhibitors significantly enhanced the bioavailability of modafinil.

Microcrystalline Preparation of Akebia Saponin D for its Bioavailability Enhancement in Rats

2015 ◽  
Vol 43 (03) ◽  
pp. 513-528 ◽  
Author(s):  
Qiao-Han Wang ◽  
Xiao-Lin Yang ◽  
Wei Xiao ◽  
Zhen-Zhong Wang ◽  
Gang Ding ◽  
...  
Keyword(s):  
Large Scale ◽  
Oral Absorption ◽  
Bone Fractures ◽  
Aqueous Solubility ◽  
Pharmacokinetic Parameters ◽  
Scanning Calorimetry ◽  
Bioavailability Enhancement ◽  
Large Scale Preparation ◽  
Scale Preparation

Akebia Saponin D (ASD) or asperosaponin VI is the most abundant constituent of the rhizome of Dipsacus asper, which has been used for the treatment of lower back pain, traumatic hematoma and bone fractures. In recent years, it was reported that ASD was a potential treatment strategy for Alzheimer's disease (AD). However, the low bioavailability of ASD limited its clinical utility. Microcrystalline preparation is one of the effective methods to improve drug absorption. The drugs prepared by different methods can present different solid forms (polymorphs), and different polymorphs have significantly different bioavailabilities. The objective of this study was to prepare ASD polymorphs using the different preparation processes and to evaluate their physicochemical properties and oral absorption. ASD-2 obtained by the antisolvent process was simpler and had higher recovery (78.5%) than that of ASD-1 by a two-step macroporous resin column separation (56.5%). The ASD polymorphs were characterized using differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The results revealed that ASD-2 existed in microcrystalline form, while ASD-1 was amorphous. Furthermore, the equilibrium solubility, dissolution in aqueous solution and pharmacokinetic parameters of the samples were determined. ASD-2 showed lower aqueous solubility than that of ASD-1 (p < 0.01). In addition, ASD-2 showed lower dissolution with only 65% of the drug released while ASD-1 had a higher dissolution with 99% of drug released at the end of the 180 min testing period. Although ASD-1 significantly increased solubility and dissolution, the AUC 0-20h of ASD-2 was 4.3 times that of the amorphous ASD-1 in vivo. Data suggest that the microcrystalline preparation of ASD-2 is not only reasonable in economy and suitable for large-scale preparation, but also a promising method to enhance bioavailability of ASD.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

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

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.

scholarly journals DEVELOPMENT OF SELF NANO-EMULSIFYING DRUG DELIVERY SYSTEM FOR AN ANTI-HYPERTENSIVE AGENT FELODIPINE: A SYSTEMATIC APPROACH FOR LIPID NANO-FORMULATION WITH IMPROVED ORAL BIOAVAILABILITY IN RATS

2020 ◽  
pp. 86-94
Author(s):  
K. TRIDEVA SASTRI ◽  
G. V. RADHA
Keyword(s):  
Droplet Size ◽  
Aqueous Solubility ◽  
Bioavailability Enhancement ◽  
Cinnamon Oil ◽  
Stability Robustness ◽  
Tween 60 ◽  
Spherical Droplets ◽  
Nano Formulation

Objective: The present study involves the development of SNEDDS employing essential oils for enhancing biopharmaceutical performance. Methods: Preliminary investigations suggested the selection of cinnamon oil as an essential oil, tween 60 as a surfactant, while transcutol HP as a cosolvent for formulating SNEDDS. Formulations evaluated for stability, robustness to dilution, and emulsification time, droplet size, zeta potential (ζ), cloud point, in vitro drug release, drug excipient compatibility, TEM, stability assessment and in vivo pharmacokinetic performance in rats. Results: All formulations were robust, stable, and revealed excellent emulsification time<40 s, with fine droplet size (11.41±2.41 nm), lower PDI (0.028-0.277). Formulation F(FLD)6 exhibited a release of 97.7% within 4h, and TEM photograph confirmed spherical droplets. The bioavailability results revealed a higher rate and extent of absorption, AUC, and Cmax for the formulations found to be 1212.4 and 355.40±13.67 (p<0.05). The results recommend that the developed formulation approach offers bioavailability enhancement of FLD. Conclusion: The study concluded that SNEDDS would be an effective formulation system in increasing the aqueous solubility and potentially bioavailability. Furthermore, it can be applied for other therapeutic categories of drugs belonging to BCS class II and IV that show comparable biopharmaceutical challenges.

scholarly journals Quality by design (QbD) based fabrication of atazanavir loaded nanostructured lipid carriers for lymph targeting: Bioavailability enhancement using chylomicron flow block model and toxicity study

2021 ◽  
Author(s):  
Vishal Gurumukhi ◽  
Sanjaykumar Bari
Keyword(s):  
High Pressure ◽  
Quality By Design ◽  
Aqueous Solubility ◽  
Relative Bioavailability ◽  
Nanostructured Lipid Carriers ◽  
Block Model ◽  
Critical Material ◽  
Bioavailability Enhancement

Abstract Atazanavir (ATV) is widely used as anti-HIV agent with poor aqueous solubility which requires fabrication of novel drug delivery system to enhance therapeutic activity and safety. For this purpose, the quality by design (QbD) based ATV loaded nanostructured lipid carriers (NLCs) to address the challenges of bioavailability and its safety on oral administration. Herein, the main objective was to identify the influencing variables for the production of quality product. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (P<0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, PXRD, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37±1.03 %) with a mechanism of Korsmeyer-Peppas model (r2 =0.925, and n=0.63). In vivo evaluation in Wistar rats showed significantly higher (p<0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.

scholarly journals Hydrophilic Sugars for Enhancing Dissolution Rate of Cilostazol: Effect of Wet Co-Processing

2020 ◽  
Vol 27 (1) ◽  
pp. 111-120
Author(s):  
Alaa Yosf Bazeed ◽  
Ahmed Nouh ◽  
Ebtessam Ahmed Essa ◽  
Gamal El Maghraby
Keyword(s):  
Aqueous Solubility ◽  
Submicron Particles ◽  
Drug Dissolution ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Swallowing Difficulties ◽  
Fast Disintegrating Tablets

Background: Cilostazol is an anti-platelets drug with considerable antithrombotic effects in vivo. Therefore, it is widely used by elderly patients. However, it suffers from poor bioavailability due to its low aqueous solubility. The objective of this work was to enhance the dissolution of cilostazol with the aim of formulating fast dissolving tablets for geriatrics and those of swallowing difficulties. Methods: Ethanol-assisted co-grinding of cilostazol with sugar-based excipients was adopted. Sucralose and mannitol were used for this purpose as hydrophilic excipient as well as taste improving agents. The obtained products were investigated regarding differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, scanning electron microscope (SEM) and in vitro drug dissolution. Fast disintegrating tablets were prepared and evaluated. Results: Thermal behavior of the developed products reflected reduced crystallinity, it also suggested possible existence of new crystalline species with sucralose. Eutexia was also suggested for mannitol mixtures, that was supported by X-ray diffraction data. SEM indicated size reduction with the deposition of the drug as submicron particles over the excipient surface. Co-processing markedly improved cilostazol dissolution compared to unprocessed drug. The optimized formulations were successively formulated into fast disintegrating tablets. Conclusion: This investigation introduced the wet grinding strategy with sugar excipients as a platform for the formulation of easy to use tablets with optimum drug release.

scholarly journals STUDIES ON BIOAVAILABILITY ENHANCEMENT OF CURCUMIN

2019 ◽  
pp. 20-25
Author(s):  
N. R. KOTAGALE ◽  
P. B. CHARDE ◽  
A. HELONDE ◽  
K. R. GUPTA ◽  
M. J. UMEKAR ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Cellular Uptake ◽  
Aqueous Solubility ◽  
Nitro Derivative ◽  
Uv Spectrophotometry ◽  
Bioavailability Enhancement ◽  
Chloride Dihydrate ◽  
Chloride Hexahydrate ◽  
Structural Analogues

Objective: The objective of the present work was to improve aqueous solubility and in vivo bioavailability of curcumin and structural analogues of curcumin such as potassium, calcium, magnesium salts and nitro derivative. Methods: Structural analogues of curcumin were prepared by reaction of curcumin with potassium chloride, magnesium chloride hexahydrate and calcium chloride dihydrate in a suitable solvent. The nitro derivative synthesized by treating curcumin with sulphuric acid and nitric acid. The prepared analogues were evaluated for melting behavior, solubility, UV spectrophotometry, partition coefficient, moisture content, cellular uptake, FTIR analysis, antimicrobial activity and in vivo bioavailability in the rat. Results: Chemical modification of curcumin increased the saturation solubility to 11.6, 16.5, 21.5, 28.0 µg/ml in calcium salt, magnesium salt, potassium salt and nitro derivative respectively, against 8.6 µg/ml of curcumin. The analogues were chemically stable as curcumin analyzed by FTIR spectrophotometry. Increased cellular uptake, as well as enhanced antimicrobial activity, was demonstrated by modified curcumin analogues. Moreover, significant improvement in plasma levels was estimated with nitro derivative. Conclusion: The present work recommends that nitration of curcumin improves aqueous solubility which may improve absorption and in vivo bioavailability.

Formulation, Optimization, in Vitro and in Vivo Investigation of Ketoprofen - Fumaric Acid Co-crystal for the Solubility Enhancement of Ketoprofen

2021 ◽  
Author(s):  
Meenakshi Bhatia ◽  
Ashwani Kumar ◽  
Vikas Verma ◽  
Snehlata Yadav ◽  
SUNITA DEVI
Keyword(s):  
Fumaric Acid ◽  
Protein Denaturation ◽  
Research Work ◽  
Molar Ratio ◽  
Scanning Calorimetry ◽  
Standard Drug ◽  
Anti Inflammatory ◽  
Analgesic Activities

Abstract The present piece of research work is framed as improving the solubility of ketoprofen by forming co-crystal using fumaric acid as a coformer. Co-crystal of ketoprofen and fumaric acid were prepared by simple solvent assisted grinding. The independent variables i.e. drug and coformer were mixed in 1:1 molar ratio and dependent variables were assumed to be solubility and % drug release. Differential scanning calorimetry, fourier transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance and scanning electron microscopy techniques were used to characterize the preparation of optimized batch of co-crystal and further, evaluated for in-vitro and in-vivo anti-inflammatory and analgesic activities. Based on results of solubility and dissolution rate studies the drug showed 4-5 fold improvement in both the properties on co-crystallisation. The values of Gibbs free energy are negative at all levels of carrier demonstrating spontaneity of drug solubilization process. The IC50 value of optimized batch of co-crystal formulation and pure drug was observed as 327.33 µg/ml and 556.11 µg/ml, respectively, demonstrating that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. In-vivo (anti-inflammatory and analgesic) activities revealed that optimized batch of co-crystal formulation delivered a rapid pharmacological response in wistar rats and albino mice when compared with standard drug.

scholarly journals Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1513
Author(s):  
Wei Wei ◽  
Veronica I. Evseenko ◽  
Mikhail V. Khvostov ◽  
Sergey A. Borisov ◽  
Tatyana G. Tolstikova ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Nmr Relaxation ◽  
Aqueous Solubility ◽  
Disodium Salt ◽  
Artificial Membrane ◽  
Scanning Calorimetry ◽  
Relaxation Methods ◽  
Pharmacokinetic Properties ◽  
Anti Inflammatory

Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the possibility of improving the solubility and the bioavailability of NIM via complexation with polysaccharide arabinogalactan (AG), disodium salt of glycyrrhizic acid (Na2GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO3. Solid dispersions (SD) have been prepared using a mechanochemical technique. The physical properties of nimesulide SD in solid state were characterized by differential scanning calorimetry and X-ray diffraction studies. The characteristics of the water solutions which form from the obtained solid dispersions were analyzed by reverse phase and gel permeation HPLC. It was shown that solubility increases for all complexes under investigation. These phenomena are obliged by complexation with auxiliary substances, which was shown by 1H-NMR relaxation methods. The parallel artificial membrane permeability assay (PAMPA) was used for predicting passive intestinal absorption. Results showed that mechanochemically obtained complexes with polysaccharide AG, Na2GA, and HP-β-CD enhanced permeation of NIM across an artificial membrane compared to that of the pure NIM. The complexes were examined for anti-inflammatory activity on a model of histamine edema. The substances were administered per os to CD-1 mice. As a result, it was found that all investigated complexes dose-dependently reduce the degree of inflammation. The best results were obtained for the complexes of NIM with Na2GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM.

scholarly journals Precise Dissolution Control and Bioavailability Evaluation for Insoluble Drug Berberine via a Polymeric Particle Prepared Using Supercritical CO2

Polymers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1198 ◽  
Author(s):  
Jingfu Jia ◽  
Kerong Zhang ◽  
Xue Zhou ◽  
Dan Zhou ◽  
Fahuan Ge
Keyword(s):  
Oral Bioavailability ◽  
Supercritical Co2 ◽  
Pharmaceutical Research ◽  
Particle Morphology ◽  
Aqueous Solubility ◽  
Dissolution Enhancement ◽  
Resonance Spectroscopy ◽  
Pharmacokinetic Studies ◽  
Scanning Calorimetry

It is still controversial whether poor aqueous solubility is the most primary reason for the low oral bioavailability of insoluble drugs. Therefore, in this study, berberine-loaded solid polymeric particles (BPs) of varied dissolution profiles with β-cyclodextrin (β-CD) as carrier were fabricated using solution-enhanced dispersion by supercritical fluids (SEDS), and the relationship between dissolution and berberine (BBR) bioavailability was evaluated. Dissolution property was controlled via particle morphology manipulation, which was achieved by adjusting several key operating parameters during the SEDS process. Characterization on BP using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction indicated that BBR was dispersed in amorphous form, while nuclear magnetic resonance spectroscopy showed that methoxy groups of BBR were included into the cavities of β-CD. In vivo pharmacokinetic studies showed that oral bioavailability increased by about 54% and 86% when the dissolution rate of BBR was increased by 51% and 83%, respectively. The entry speed of BBR into the bloodstream was also advanced with the degree of dissolution enhancement. It seemed that dissolution enhancement gave positive effect to the oral bioavailability of berberine, but this might not be the crucial point. Meanwhile, supercritical CO2 technology is a promising method for pharmaceutical research due to its advantages in regulating drug-dosage properties.

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