scholarly journals Rosuvastatin cocrystals: an attempt to modulate physicochemical parameters

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Venkata Deepthi Vemuri ◽  
Srinivas Lankalapalli
Keyword(s):  
Physicochemical Properties ◽  
Dissolution Rate ◽  
Functional Groups ◽  
Preliminary Investigation ◽  
Scale Up ◽  
Solvent Evaporation ◽  
Molar Ratio ◽  
The Novel ◽  
Formulation Development ◽  
Hydrogen Bond Interaction

Abstract Background The meager physicochemical properties like low solubility and low dissolution rate of rosuvastatin calcium remain as an obstruction for formulation development. In the present work, we explore the evolution of rosuvastatin cocrystal, which may offer the synergetic physico-chemical properties of the drug. Cocrystal crafting depends on two possible intermolecular interactions; heteromeric and the homomeric selection of compounds with complementary functional groups are contemplated as a possible cause of supramolecular synthons in cocrystal formation. Specifically, cocrystals of rosuvastatin with l-asparagine and l-glutamine with molar ratio (1:1) were fabricated by using slow solvent evaporation and slow evaporation techniques. Novel cocrystals of rosuvastatin-asparagine (RSC-C) and rosuvastatin-glutamine (RSC-G) cocrystals obtained by slow solvent evaporation were utilized for preliminary investigation and further scale-up was done by using the solvent evaporation technique. Results The novel cocrystals showed a new characteristic of powder X-ray diffraction, thermograms of differential scanning calorimetry, 1H liquid FT-NMR spectra, and scanning electron microscopy. These results signify the establishment of intermolecular interaction within the cocrystals. In both the novel cocrystals, rosuvastatin was determined to be engaged in the hydrogen bond interaction with the complementary functional groups of l-asparagine and l-glutamine. Compared with the pure rosuvastatin, RSC-C and RSC-G cocrystal showed 2.17-fold and 1.60-fold improved solubility respectively. The dissolution test showed that the RSC-C and RSC-G cocrystal exhibited 1.97-fold and 1.94-fold higher dissolution rate than the pure rosuvastatin in pH6.8 phosphate buffer respectively. Conclusion Modulation in the chemical environment, improvement in the solubility, and dissolution rate demonstrated the benefit of co-crystallization to improve the physicochemical properties of the drug. Graphical abstract

scholarly journals A novel drug–drug coamorphous system without molecular interactions: improve the physicochemical properties of tadalafil and repaglinide

RSC Advances ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 565-583 ◽  
Author(s):  
Meiling Su ◽  
Yanming Xia ◽  
Yajing Shen ◽  
Weili Heng ◽  
Yuanfeng Wei ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Molecular Interactions ◽  
Solvent Evaporation ◽  
Molar Ratio ◽  
Solvent Evaporation Method ◽  
Evaporation Method ◽  
Novel Drug

The coamorphous tadalafil–repaglinide (molar ratio, 1 : 1) prepared by solvent-evaporation method significantly improve the physicochemical properties of tadalafil and repaglinide.

scholarly journals SOLUBILITY ENHANCEMENT, FORMULATION DEVELOPMENT AND EVALUATION OF IMMEDIATE RELEASE TABLET OF ANTIHYPERTENSIVE DRUG TADALAFIL

2018 ◽  
Vol 8 (5) ◽  
pp. 294-302
Author(s):  
Mayuri Sisodiya ◽  
Ravindranath Saudagar
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Immediate Release ◽  
Solvent Evaporation ◽  
Wet Granulation ◽  
Phase Solubility ◽  
Formulation Development ◽  
Poloxamer 188 ◽  
Sodium Starch Glycolate ◽  
Release Tablet

The objective of the study was to enhance the solubility and dissolution rate of Tadalafil using hydrophilic carriers such as PVP K-30, Poloxamer 188, Sodium starch glycolate and compatibility study of Tadalafil with different polymers by FTIR. Characterization of solid dispersion-FTIR, DSC and phase solubility analysis was study to improve the oral bioavailability. Formulation and evaluation of immediate release tablets prepare from solubility enhanced Tadalafil. Among the various approaches Solvent evaporation has gained good acceptance in recent years in the industry for enhancing the solubility and dissolution rate of poorly soluble drugs. Poloxamer 188 used as polymer as it is good solubilizing agent. As per the phase solubility studies, a 32 factorial study were used to prepare the immediate release tablet and evaluated for the interactions and in vitro drug release. Sodium Starch Glycolate and PVP used as superdisintegrants. The solubility of tadalafil in selected ratios containing tadalafil and Poloxamer 188 solid dispersion prepared by solvent evaporation was determined. From the various ratios 1:0.5 was resulted in a much higher enhancement (9.75folds). Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) studies conducted, explain overall drug and excipients compatibility. More than 90% of tadalafil was released from IR tablet within 30 min. There is enhancement of the solubility rate if tadalafil by solid dispersion with Poloxamer 188 prepared by solvent evaporation method. The compatibility studies of the drug and polymers showed that there was no incompatibility between them. Wet granulation method showed that, the desired flow properties for the compression into tablets. Tablets were prepared using wet granulation method resulted into simple, cheap, more suitable method for the manufacturing immediate release dosage form.

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

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
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.

Mango (Magnifera indica) seed oil grown in Dilla town as potential raw material for biodiesel production using NaOH- a homogeneous catalyst

2019 ◽  
Author(s):  
Chem Int
Keyword(s):  
Diesel Engine ◽  
Physicochemical Properties ◽  
Seed Oil ◽  
Methyl Esters ◽  
Pollution Prevention ◽  
Raw Material ◽  
Biodiesel Production ◽  
Molar Ratio ◽  
Homogeneous Catalyst ◽  
Minimal Amount

Biodiesel produced by transesterification process from vegetable oils or animal fats is viewed as a promising renewable energy source. Now a day’s diminishing of petroleum reserves in the ground and increasing environmental pollution prevention and regulations have made searching for renewable oxygenated energy sources from biomasses. Biodiesel is non-toxic, renewable, biodegradable, environmentally benign, energy efficient and diesel substituent fuel used in diesel engine which contributes minimal amount of global warming gases such as CO, CO2, SO2, NOX, unburned hydrocarbons, and particulate matters. The chemical composition of the biodiesel was examined by help of GC-MS and five fatty acid methyl esters such as methyl palmitate, methyl stearate, methyl oleate, methyl linoleate and methyl linoleneate were identified. The variables that affect the amount of biodiesel such as methanol/oil molar ratio, mass weight of catalyst and temperature were studied. In addition to this the physicochemical properties of the biodiesel such as (density, kinematic viscosity, iodine value high heating value, flash point, acidic value, saponification value, carbon residue, peroxide value and ester content) were determined and its corresponding values were 87 Kg/m3, 5.63 Mm2/s, 39.56 g I/100g oil, 42.22 MJ/Kg, 132oC, 0.12 mgKOH/g, 209.72 mgKOH/g, 0.04%wt, 12.63 meq/kg, and 92.67 wt% respectively. The results of the present study showed that all physicochemical properties lie within the ASTM and EN biodiesel standards. Therefore, mango seed oil methyl ester could be used as an alternative to diesel engine.

Influence of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin on Enhancement of Solubility and Dissolution of Isradipine

2017 ◽  
Vol 10 (3) ◽  
pp. 3752-3757
Author(s):  
Narendar D ◽  
Ettireddy S
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Molecular Complexes ◽  
In Vitro Dissolution ◽  
Molar Ratio ◽  
Phase Solubility ◽  
Cyclodextrin Complexation

The content of this investigation was to study the influence of β-cyclodextrin and hydroxy propyl-β-cyclodextrin complexation on enhancement of solubility and dissolution rate of isradipine. Based on preliminary phase solubility studies, solid complexes prepared by freeze drying method in 1:1 molar ratio were selected and characterized by DSC for confirmation of complex formation. Prepared solid dispersions were evaluated for drug content, solubility and in vitro dissolution. The physical stability of optimized formulation was studied at refrigerated and room temperature for 2 months. Solid state characterization of optimized complex performed by DSC and XRD studies.  Dissolution rate of isradipine was increased compared with pure drug and more with HP-β-CD inclusion complex than β-CD. DSC and XRD analyzes that drug was in amorphous form, when the drug was incorporated as isradipine β-CD and HP-β-CD inclusion complex. Stability studies resulted in low or no variations in the percentage of complexation efficiency suggesting good stability of molecular complexes. The results conclusively demonstrated that the enhancement of solubility and dissolution rate of isradipine by drug-cyclodextrin complexation was achieved.   

Solubility Enhancement of the Poorly Water-Soluble Antiulcer Drug Famotidine by Inclusion Complexation

2013 ◽  
Vol 6 (1) ◽  
pp. 1983-1989 ◽  
Author(s):  
Shabnam Ain ◽  
V Gupta ◽  
Babita K ◽  
Q Ain ◽  
J Dahiya
Keyword(s):  
Inclusion Complex ◽  
Dissolution Rate ◽  
Phosphate Buffer ◽  
Physical Mixture ◽  
Water Soluble ◽  
Molar Ratio ◽  
Phase Solubility ◽  
Distilled Water ◽  
Physicochemical Interaction ◽  
Mixture Phase

Aqueous solubility is a critical factor for optimum drug delivery. In the present study, we investigated the potential of drug-cyclodextrin complexation as an approach for improving the solubility and bioavailability of famotidine, an H2-receptor antagonist and acid reducing drug which has poor solubility and bioavailability. Solubility improvement of drug by β-cyclodextrin was done by simple complexation approach using physical, kneading and co-precipitation methods and compared with physical mixture. Phase solubility profile indicated that the solubility of famotidine was significantly increased in presence of β-cyclodextrin and shows a linear graph with β-cyclodextrin indicating formation of inclusion complexes in a 1:1 molar ratio. β-Cyclodextrin-famotidine mixture have maximum stability constant 1477.6 M-1. The inclusion complex ratio 1:1 of kneading mixture was selected based on drug release profile and compared with physical mixture. Further characterization was done by  using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) to identify the physicochemical interaction between drug and carrier and its effect on dissolution. Dissolution rate studies for selected inclusion complex was performed in 0.1 N HCl (pH 1.2), phosphate buffer (pH 7.5) and distilled water (pH 6.8) and compared these to pure drug profile which was found to be 2.34 fold increase in distilled water, 1.83 fold in HCl and 2.01 fold in phosphate buffer (pH 7.5). These results suggest that the kneaded complex of famotidine with β-cyclodextrin as hydrophilic complexation agent can substantially enhance the solubility and dissolution rate. Such complex has promising potential to improve the bioavailability of famotidine.  

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

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.

Azithromycin nanosuspension preparation using evaporative precipitation into aqueous solution (EPAS) method and its comparative dissolution study

2020 ◽  
Vol 17 ◽  
Author(s):  
Mohammad Hossain Shariare ◽  
Tonmoy Kumar Mondal ◽  
Hani Alothaid ◽  
Md. Didaruzzaman Sohel ◽  
MD Wadud ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Particle Size ◽  
Dissolution Rate ◽  
Average Particle Size ◽  
Scale Up ◽  
Average Particle ◽  
Total Drug ◽  
Residual Solvent ◽  
Dissolution Study ◽  
Drug Content

Aim: EPAS (evaporative precipitation into aqueous solution) was used in the current studies to prepare azithromycin nanosuspensions and investigate the physicochemical characteristics for the nanosuspension batches with the aim of enhancing the dissolution rate of the nanopreparation to improve bioavailability. Methods: EPAS method used in this study for preparing azithromycin nanosuspension was achieved through developing an in-house instrumentation method. Particle size distribution was measured using Zetasizer Nano S without sample dilution. Dissolved azithromycin nanosuspensions were also compared with raw azithromycin powder and commercially available products. Total drug content of nanosuspension batches were measured using an Ultra-Performance Liquid Chromatography (UPLC) system with Photodiode Array (PDA) detector while residual solvent was measured using gas chromatography (GC). Results: The average particle size of azithromycin nanosuspension was 447.2 nm and total drug content was measured to be 97.81% upon recovery. Dissolution study data showed significant increase in dissolution rate for nanosuspension batch when compared to raw azithromycin and commercial version (microsuspension). The residual solvent found for azithromycin nanosuspension is 0.000098023 mg/ mL or 98.023 ppb. Conclusion: EPAS was successfully used to prepare azithromycin nanoparticles that exhibited significantly enhanced dissolution rate. Further studies are required to scale up the process and determine long term stability of the nanoparticles.

scholarly journals Physico-Chemical and Pharmaco-Technical Characterization of Inclusion Complexes Formed by Rutoside with β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin Used to Develop Solid Dosage Forms

Processes ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 26
Author(s):  
Teodora Balaci ◽  
Bruno Velescu ◽  
Oana Karampelas ◽  
Adina Magdalena Musuc ◽  
George Mihai Nițulescu ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Molar Ratio ◽  
Mechanical Resistance ◽  
Direct Compression ◽  
Active Ingredients ◽  
Compression Process ◽  
Antioxidant Power

The aim of our study was to obtain rutoside (RUT) inclusion complexes in β-cyclodextrin (β-CD) and in hydroxypropyl-β-cyclodextrin (HP-β-CD), in a 1:1 molar ratio, using the lyophilization method of complexation in solution. The complexes were confirmed and characterized, in comparison with the raw materials and their simple physical mixtures, by SEM, DSC, and FT-IR analyses. The antioxidant activity of the compounds was assessed by using the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and 2’-azino-bis(3-ethylbenzothiazolin-6-sulfonic) acid (ABTS) radicals, determining the radical scavenging activity, and by ferric reducing antioxidant power (FRAP) assay. The results revealed superior antioxidant ability for the inclusion complexes towards rutoside alone. The inclusion complexes were used as active ingredients in formulations of immediate-release tablets. The preformulation studies were performed on the powders for direct compression obtained after mixing the active ingredients with the excipients (Avicel PH 102, Polyplasdone XL-10, magnesium stearate, and talc). The materials were assessed for particle size, flowability, compressibility, and moisture content, establishing they are suitable for a direct compression process. The tablets were characterized regarding their pharmaco-technical properties and the results proved that the formulations lead to high-quality delivery systems, showing a good mechanical resistance with a low friability, excellent disintegration times, and satisfying dissolution rate. The performances were very similar for both formulations and the physico-mechanical properties of the tablets are not influenced by type of the used cyclodextrin, but the RUT- HP-β-CD tablets presented a higher dissolution rate.

A chemoinformatic analysis of atoms, scaffolds and functional groups in natural products

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Joelle Ngo Hanna ◽  
Boris D. Bekono ◽  
Luc C. O. Owono ◽  
Flavien A. A. Toze ◽  
James A. Mbah ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Physicochemical Properties ◽  
Functional Groups ◽  
Atomic Composition ◽  
Synthetic Compounds ◽  
Chemical Libraries ◽  
Synthetic Drugs ◽  
Drugs Analysis ◽  
Chemical Class

Abstract In the quest to know why natural products (NPs) have often been considered as privileged scaffolds for drug discovery purposes, many investigations into the differences between NPs and synthetic compounds have been carried out. Several attempts to answer this question have led to the investigation of the atomic composition, scaffolds and functional groups (FGs) of NPs, in comparison with synthetic drugs analysis. This chapter briefly describes an atomic enumeration method for chemical libraries that has been applied for the analysis of NP libraries, followed by a description of the main differences between NPs of marine and terrestrial origin in terms of their general physicochemical properties, most common scaffolds and “drug-likeness” properties. The last parts of the work describe an analysis of scaffolds and FGs common in NP libraries, focusing on huge NP databases, e.g. those in the Dictionary of Natural Products (DNP), NPs from cyanobacteria and the largest chemical class of NP – terpenoids.

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