Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic properties

Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic propertiesCelecoxib spherical agglomerates were prepared with polyvinylpyrrolidone (PVP) using acetone, water and chloroform as solvent, non-solvent and bridging liquid, respectively. The agglomerates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), IR spectroscopic studies and scanning electron microscopy (SEM). The IR spectroscopy and DSC results indicated the absence of any interactions between drug and additives. XRD studies showed a decrease in crystallinity in agglomerates. The crystals exhibited significantly improved micromeritic properties compared to pure drug. The loading efficiency (% or mg drug per 100 mg crystals) was in the range of 93.9 ± 2.3 and 97.3 ± 1.3% (n = 3) with all formulations. The aqueous solubility and dissolution rate of the drug from crystals was significantly (p < 0.05) increased (nearly two times). The solubility andin vitrodrug release rates increased with an increase in PVP concentration (from 2.5 to 10%). The SEM studies showed that the crystal posseses a good spherical shape with smooth and regular surface.

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

Pharmaceutical Sciences ◽

10.34172/ps.2020.64 ◽

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.

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IMPROVEMENT OF DISSOLUTION RATE OF VALSARTAN BY SOLID DISPERSION SYSTEM USING D(−) MANNITOL

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i3.16171 ◽

2017 ◽

Vol 10 (3) ◽

pp. 288 ◽

Cited By ~ 1

Author(s):

Erizal Zaini ◽

Salman Umar ◽

Nurhidayah Nurhidayah

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

In Vitro Dissolution ◽

Type I ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Dispersion System ◽

Grinding Technique

ABSTRACTObjective: To improve dissolution rate of valsartan from solid dispersion system of valsartan and D(−) mannitol using co-grinding approach.Methods: Valsartan solid dispersion with different ratio of D(−) mannitol (1:1; 1:3 and 1: 5) were prepared by co-grinding method. Solid statecharacterization of the solid dispersion system was evaluated in term of crystallographic properties (powder X-ray diffraction), thermal behavior(differential scanning calorimetry [DSC]) and morphology (scanning electron microscope). The profile of dissolution rate was examined using USPdissolution apparatus type I at a temperature of 37±0.5°C.Results: Based on thermal analysis DSC and powder X-ray diffraction analysis, valsartan was transformed from semicrystalline phase to amorphousstate as indicated by the disappearance of its melting endothermic peaks and the characteristic diffraction peaks. The in vitro dissolution rate studyrevealed that all solid dispersion system showed significant increase in dissolution rate compared with the intact valsartan.Conclusion: Solid dispersion of valsartan with D(−) mannitol prepared by co-grinding technique has successfully improved the dissolution ratecompared with intact valsartan.Keywords: Valsartan, D(−) mannitol, Solid dispersion, Co-grinding, Dissolution rate.

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PCL/PHBV Microparticles as Innovative Carriers for Oral Controlled Release of Manidipine Dihydrochloride

The Scientific World JOURNAL ◽

10.1155/2014/268107 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 11

Author(s):

Fernanda Malaquias Barboza ◽

Willian Moreira Machado ◽

Luiz Renato Olchanheski Junior ◽

Josiane Padilha de Paula ◽

Sônia Faria Zawadzki ◽

...

Keyword(s):

Controlled Release ◽

Animal Studies ◽

Average Particle Size ◽

Spherical Shape ◽

Average Particle ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Chemically Modified ◽

Diffraction Patterns

Microparticles of poly(ε-caprolactone) (PCL) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) containing manidipine dihydrochloride (MAN) were successfully prepared by the simple emulsion/solvent evaporation method. All formulations showed loading efficiency rates greater than 80% and average particle size less than 8 μm. Formulations had spherical shape with smooth and porous surface for PCL and PHBV, respectively. According to Fourier-transform infrared spectroscopy, initial components were not chemically modified during microencapsulation. X-ray diffraction patterns and differential scanning calorimetry demonstrated that this process led to drug amorphization.In vitrodissolution studies showed that all microparticles prolonged MAN release, mainly which one obtained using PCL that contained 5% of drug loaded (PCL-M5). Animal studies demonstrated that formulationPCL-M5was able to keep the variation of mean arterial pressure after phenylephrine administration up to 24 hours. These data confirmed the sustained antihypertensive effect of the investigated microparticles. Results provided an experimental basis for using formulationPCL-M5as a feasible carrier for oral controlled release of MAN intended for treating high blood pressure.

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Enhancement of solubility and dissolution rate of ebastine fast-disintegrating tablets by solid dispersion method

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i9.1 ◽

2020 ◽

Vol 19 (9) ◽

pp. 1797-1805

Author(s):

Nayyer Islam ◽

Muhammad Irfan ◽

Nasir Abbas ◽

Haroon Khalid Syed ◽

Muhammad Shahid Iqbal ◽

...

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Aqueous Solubility ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Disintegration Time ◽

Kneading Method ◽

The Impact ◽

Fast Disintegrating Tablets

Purpose: To investigate the efficiency of different solubilizing agents in improving solubility as well as dissolution rate of ebastine (a BCS class II drug) by incorporating prepared solid dispersion into fast disintegrating tablets.Method: The solubility of ebastine was determined in distilled water, lipids and solubilizing agents. Subsequently, the binary solid dispersions were prepared by kneading method using varying weight ratios of ebastine and solubilizing agents. The solid dispersions were then incorporated into fast disintegrating tablets (SD-FDT). Central composite rotatable design (CCD) was used to determine the impact of super disintegrating agents on disintegration time and friability of tablets. The solubility and dissolution rate of developed SD-FDT were compared with a marketed brand. The solid dispersion particles were characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder x-ray diffraction (P-XRD) and scanning electron microscopy (SEM).Results: The saturated solubility of pure ebastine in water was 0.002 ± 0.041 mg/ml while the aqueous solubility of EBT/poloxamer solid dispersion SET3 (P) was 0.018 ± 2.510 mg/ml; on the other hand, EBT/soluplus solid dispersion SET1(S) has an aqueous solubility of 0.242 ± 1.390 mg/ml. Within 30 min, drug release was 14.00 ± 1.77, 78.00 ± 2.31 and 98.70 ± 2.54 % from pure EBT, SET3 (P) and SET1(S), respectively.Conclusion: The solubility and dissolution rate of ebastine has been successfully enhanced by incorporating its solid dispersion in fast-disintegrating tablets (SD-FDT). Keywords: Ebastine, Solid dispersion, Poloxamer 188, Soluplus, Solubility, Dissolution

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ENHANCEMENT SOLUBILITY AND DISSOLUTION RATE OF PARACETAMOL AND IBUPROFEN BY COAMORPHOUS PARTICLES USING MICROWAVE TECHNIQUE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i11.34589 ◽

2019 ◽

pp. 155-162

Author(s):

ANILKUMAR SHINDE ◽

NAMDEO JADHAV ◽

OJAS SHINDE ◽

PRAVIN PATIL

Keyword(s):

Dissolution Rate ◽

Aqueous Solubility ◽

Class Iii ◽

Dose Ratio ◽

Scanning Calorimetry ◽

Maximum Increase ◽

Dsc Studies ◽

Microwave Assisted ◽

Microwave Assisted Method

Objective: The objective of the present study was to the preparation of a coamorphous (COAM) system of paracetamol (PA) (Biopharmaceutics Classification System [BCS] Class-III) and ibuprofen (IB) (BCS Class-II) for enhancement of solubility and dissolution of IB. Methods: The COAM system was prepared by chemical electric magnetic field microwave-assisted method. Several batches with different concentrations of COAM PA and IB were prepared at constant temperature, pressure, and holding time. Solubility studies were carried out in different pH condition and the batch, which show the highest increase in solubility 98.00%. COAM samples were characterized by solubility, dissolution, Fourier transform infrared (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC) studies. Results: FTIR results showed evidence of molecular interactions between both the drugs. Maximum increase in aqueous solubility of IB was seen 500:200 mg dose ratio (COAM) batch E in phosphate buffer 7.4. The COAM system increased solubility of IB about 98.70%. The solubility and dissolution rate of IB were also enhanced. In vitro drug release study, 100% of the drug was released within 120 min. Thus, saturation solubility and dissolution rate of IB were found significant improved unlike PA. XRD and DSC results confirmed amorphization of IB. FTIR results evidenced hydrogen bonding interactions between both the drugs. In accelerated stability studies, powder XRD and DSC results demonstrated insignificant changes, thus confirming successful stabilization of IB by PA. Conclusion: Hence, it concluded that the study of COAM of PA and IB successfully prepared by microwave-assisted method to enhance solubility, dissolution, stability, and bioavailability.

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Formulation and Characterization of Itraconazole as Nanosuspension Dosage Form for Enhancement of Solubility

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

10.31351/vol28iss2pp124-133 ◽

2019 ◽

Vol 28 (2) ◽

pp. 124-133

Author(s):

Asmaa M. Rashid ◽

Shaimaa N. Abdal-Hammid

Keyword(s):

Fourier Transforms ◽

Fungal Infections ◽

Tween 80 ◽

Aqueous Solubility ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Nanoprecipitation Method ◽

Systemic Infections

Abstract Itraconazole is a triazole antifungal given orally for the treatment of oropharyngeal and vulvovaginal candidiasis, for systemic infections including aspergillosis, candidiasis, and for the prophylaxis of fungal infections in immunocompromised patients. The study aimed to formulate a practical water-insoluble Itraconazole, with insufficient bioavailability as nanosuspension to increase aqueous solubility and improve its dissolution and oral bioavailability. Itraconazole nanosuspension was produced by a solvent-antisolvent nanoprecipitation method in the presence of different stabilisers (Poloxamer-188, HPMCE5) at different ratios with the drug alone or combination with surfactant(tween 80, SLS). The results exhibit that the particle sizes of all prepared itraconazole formulations were in the nano size. The best formula (F6) has a particle size. ( 42 ) nm and Zeta potential of (- 21.86 ) mV. In vitro cumulative release from the nanosuspension was (88 %) at (30) min when compared to the pure drug (13%) and lyophilized nanoparticles (98.2%) at (30)min. Effect of different parameters was investigated. Fourier transforms infrared spectroscopy(FTIR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD), Scanning electron microscope( SEM) was done for the optimized nanoparticles prepared by lyophilization technique Thus, Nanosuspension appears to be an encouraging approach to formulate Itraconazole nanosuspension with high solubility and dissolution rate. Keywords: Itraconazole, Nanoprecipitation method, Nanosuspension

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PREPARATION OF ACYCLOVIR-NICOTINAMIDE COCRYSTAL BY SOLVENT EVAPORATION TECHNIQUE WITH VARIATION OF SOLVENT

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i3.16149 ◽

2017 ◽

Vol 10 (3) ◽

pp. 283

Author(s):

Roisah Nawatila ◽

Agnes Nuniek W ◽

Siswandono Siswodihardjo ◽

Dwi Setyawan

Keyword(s):

Acetic Acid ◽

Dissolution Rate ◽

Glacial Acetic Acid ◽

Molar Fraction ◽

Solvent Evaporation ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Evaporation Technique ◽

Ft Ir

ABSTRACTObjective: This research aims to prepare cocrystal of acyclovir (ACV)-nicotinamide (NCT) by solvent evaporation with a variation of solvent (ethanol,glacial acetic acid, and HCl 0.1 N) to improve the bioavailability of ACV as an antiviral drug.Methods: Cocrystal were developed by solvent evaporation with 1:1 molar fraction, using variation of solvent such as ethanol, glacial acetic acid, andHCl 0.1 N. Further, the prepared ACV-NCT cocrystal were characterized for differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD),Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), and in vitro dissolution.Results: DSC thermogram showed that ACV-NCT cocrystal in ethanol and glacial acetic acid exhibited new endothermic peak at 221.16°C and216.40°C, whereas no peaks were found for HCl 0.1 N. PXRD diffractogram showed that ACV-NCT cocrystal in ethanol exhibited new diffraction peaksat 2θ 5.9°; 9.2°; dan 13.3°, whereas no peaks were found for glacial acetic acid and HCl 0.1 N. FT-IR characterization of ACV-NCT cocrystal in ethanolshowed disappearance of transmission peaks at 3373/cm indicating the loss of NH bands of NCT. Furthermore, C=O of ACV and NCT were observed at1693/cm, and 1666/cm indicated a formation of hydrogen bonding between ACV and NCT. SEM micrographs showed that cocrystals have a differentshape compared to ACV and NCT. DE15 showed that there was a significant increase of ACV-NCT cocrystal dissolution rate in ethanol compared to thephysical mixture and ACV.Conclusion: The study concludes that ACV-NCT cocrystal in ethanol were successfully formed and the dissolution rate of ACV can increase significantly(α=0.05).Keywords: Cocrystallization, Solvent, Acyclovir, Nicotinamide, Solvent evaporation.

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Formulation, Characterization and Antihelminthic Activity Testing of Nitazoxanide Superporous Hydrogel Tablets

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i3-s.4130 ◽

2020 ◽

Vol 10 (3-s) ◽

pp. 26-36

Author(s):

S. Vinaya Srikala ◽

Nagam Santhi Priya ◽

Rama Rao Nadendla

Keyword(s):

Drug Release ◽

Spectroscopic Studies ◽

High Dose ◽

Drug Release Profile ◽

Scanning Calorimetry ◽

Superporous Hydrogels ◽

Ft Ir ◽

Ir Spectroscopic ◽

Superporous Hydrogel

In the pharmaceutical field controlled release products have the ability to maintain desired medicament concentration or a longer period of time. Certain drugs are relatively insoluble in water and have high dose requirements that render unsuitable formulation difficulties in sustained release formulations. Nitazoxanide which is a high dose water insoluble antiprotozoal drug was formulated with the aim. To modulate gastro-retentive dosage form based on the superporous hydrogel composites. Foaming technique was used in the preparation of SPH composites. The superporous hydrogels were extremely sensitive to pH of swelling media and good porosity. Superporous hydrogels tablets of nitazoxanide showed good pre-compressional and post-compressional properties. Formulation X is the best formulation containing chitosan, polyvinyl alcohol, formaldehyde, exhibited good swelling ratio. The compatibility studies were performed by Fourier Transform Infrared (FT-IR) Spectroscopic Studies, Differential Scanning Calorimetry Studies (DSC). All formulations were evaluated for stability, drug content, and kinetic drug release & in-vitro drug release profile. It was concluded that the proposed gastro-retention drug delivery provides a different supply of nitazoxanide directly to the stomach. Keywords: Nitazoxanide, Anti protozoal, foaming technique, Chitosan

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Artemether-Soluplus Hot-Melt Extrudate Solid Dispersion Systems for Solubility and Dissolution Rate Enhancement with Amorphous State Characteristics

Journal of Pharmaceutics ◽

10.1155/2013/151432 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 3

Author(s):

Ritesh A. Fule ◽

Tarique S. Meer ◽

Ajay R. Sav ◽

Purnima D. Amin

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Amorphous State ◽

Polymer Melt ◽

Aqueous Solubility ◽

Dissolution Profile ◽

Scanning Calorimetry ◽

Peg 400 ◽

Hot Melt

This work studied artemether (ARTM) solid dispersion (SD) formulation using mixture of polymer excipient Soluplus, PEG 400, Lutrol F127, and Lutrol F68 melts at temperatures lower than the melting point of ARTM using a laboratory-size, single-screw rotating batch extruder. The effects of three surfactants PEG 400, Lutrol F127, and Lutrol F68 and parameters like mixing temperature, screw rotating speed, and residence time were systematically studied. SEM, XRD, and FT-IR were employed to investigate the evolution of ARTM’s dissolution into the molten excipient. Differential scanning calorimetry (DSC) was used to quantitatively study the melting enthalpy evolution of the drug. The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug. It was concluded that the dissolution of the drug in the polymer melt is a convective diffusion process and that laminar distributive mixing can significantly enhance the dissolution rate. The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced. In vitro antimalarial studies revealed marked improvement in IC50 values. Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM.

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