Solid Dispersions Of Ibuprofen Research Articles

Formulation and characterization of ibuprofen solid dispersions using native and modified starches

Background: Ibuprofen is an anti-inflammatory analgesic drug that is weakly water-soluble with a poor bioavailability.Objectives: The aim of this study is to formulate ibuprofen solid dispersions by solvent evaporation method using natural polymers (native cassava and genetically modified cassava (GMS), Cassava nanocrystal and corn starches) as possible hydrophilic carriers at varying weight proportions to optimize ibuprofen solubility and dissolution.Material and Methods: Solvent evaporation method was used to formulate the ibuprofen solid dispersions at different drug polymer ratios. The pure drug and solid dispersions were characterized using Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffractometer (XRD), particle size, and in vitro drug release.Results: Solid dispersions formulated with starch nanocrystals showed the highest solubility. All solid dispersions prepared with drug:polymer ratio 1:2 generally showed highest solubility. According to the FTIR, the chemical structure of ibuprofen remained intact in the amorphous solid dispersion, but the structure changed from crystalline to amorphous, according to the XRD and the DSC also confirmed this. The scanning electron microscopy showed the solid dispersions were more porous than the pure drug. Higher dissolution rate was observed with nanocrystal solid dispersions with T50 (time required for 50% of the medication to be released) between 1.8 and 4.1 minutes.Conclusion: This study has shown that using these natural polymers increased the solubility and dissolution rate of ibuprofen.

Effect of gelling agent and penetration enhancer on the release rate of ibuprofen-PEG 6000 solid dispersion from gel preparations

Introduction: Ibuprofen is a non-steriodal anti-inflammatory drug which shows low bioavailability. For gel preparations it is important to increase the release rate of ibuprofen by using solid dispersion systems. Objective: To obtain the optimum release rate of ibuprofen-PEG 6000 solid dispersion from gel, by optimising the gelling agent and the penetrating enhancers. Method: Determination of gelling agent was carried out by comparing the ibuprofen release flux. The gel formulation with the best release flux will be used in the determination of penetrating enhancer to obtain the optimum release flux, by using a two-factor factorial design. Result: HPMC showed the highest release flux (339.5 g/cm2min). The results showed an increase in the release flux (489.4 g/cm2min) in the optimum formula with 39.9% propylene glycol and 3.3% isopropyl myristate. Conclusion: The increase in the ibuprofen solid dispersion release flux has been carried out using HPMC, and propylene glycol-isopropyl myristate as a penetrating enhancer.

Development and Characterization of Ibuprofen Solid Dispersion for Solubility and Dissolution improvement using a binary carrier system consisting of D- Mannitol - Polyethylene Glycol 6000

Background: Adequate drug bioavailability is a major problem in most solid dosage formulations. Recent works reported enhanced solubility and dissolution using a carrier. This study was carried out to enhance the solubility and dissolution of ibuprofen using a binary carrier system. Method: Solid dispersions (SD) of ibuprofen were prepared using PEG 6000 and D (-) mannitol in difffferent ratios (1:0:4, 1:1:3, 1:2:2, 1:3:1, and 1:4:0) by the fusion method. Results: Percentage yield of SD was between 96% and 99% and content analysis revealed 100 % drug content. All batches of SD showed better solubility characteristics than Ibuprofen alone or its physical mixtures. The SD batch 3, ratio 1:2:2 with equal amount of PEG and mannitol possessed the best solubility characteristic and drug release profifile with T50% at 17 min. FTIR spectral and DSC thermograms of SDs showed no interaction between the carriers and ciproflfloxacin. Conclusion: The SD3 formulated with 20 % ibuprofen, 40 % mannitol and 40 % PEG 6000 possessed better solubility and dissolution is therefore recommended

Ibuprofen-loaded centrifugally spun microfibers for quick relief of inflammation in rats

The conventional dosage forms (tablets, capsules) of ibuprofen have less potential in the suppression of pain and inflammation due to their slow dissolution rates and lower bioavailability. The aim of this study was to fabricate fibrous solid dispersion of ibuprofen for improved dissolution rate and quick therapeutic action. Drug-loaded microfibers were fabricated using centrifugal melt spinning (CMS) technique from the physical mixture of sucrose, ibuprofen and a hydrophilic polymer, PVP. These fibers were characterized by SEM, PXRD, DSC, and FTIR spectroscopy. The selected formulation was also pressed into tablets by direct compression method followed by its in vitro and in vivo characterization. The production yield of fibers was 75 ± 2% with an average diameter of 15 ± 5 µm. The drug loading efficiency (DLE) was 85 ± 5%. The tablets dissolved rapidly (<40 s). In vitro dissolution studies have shown >85% of ibuprofen dissolved from tablet within first 2 min which was ∼5 times quicker than drug alone. Dissolution efficiency has improved from 0.63 of ibuprofen to 0.95 of that in fibers with ∼7 times reduction in mean dissolution time. PXRD, and DSC have shown the amorphous state of ibuprofen in the formulation and FTIR spectra demonstrated no interaction of drug with excipients. In vivo anti-inflammatory studies using rabbits revealed a significant (p < 0.05) reduction in paw volume (mm) in the groups treated with fibrous formulation. This study concludes that microfibers produced by centrifugal melt spinning have improved dissolution rates and bioavailability of ibuprofen. Incorporation of polymer in the formulations improves the production yield and drug loading efficiency of microfibers.

Facile preparation of solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone and photopolymerization

Drug solid dispersions improve the dissolution of drugs in aqueous media for enhancement of oral bioavailability. The current preparation methods of drug solid dispersions mainly involve the evaporation of solvents or the melting of drugs and matrix. Here, we create a new and simple method for the preparation of drug solid dispersions by dissolving drugs in N-vinyl-2-pyrrolidone (NVP) and then NVP photopolymerization. A variety of drugs were explored to find whether they were suitable for this method and only some of them were soluble in NVP and formed transparent and hard solid dispersions, including fluconazole, ketoconazole, bifonazole, miconazole nitrate, sulfamethoxazole, aspirin, ibuprofen and artesunate. The formation of photocuring solid dispersions was highly related to the free radical scavenging function of drugs. Those drugs with strong free radical scavenging capability, including curcumin, resveratrol, quercetin, genistein, puerarin, nicergoline, olanzapine, indomethacin, did not form solid dispersions. They scavenged 2,2-diphenyl-1-picrylhydrazyl free radicals, which was demonstrated by ultraviolet spectrometry and electron spin resonance. The scavenging of free radicals stopped the chain polymerization of NVP. The Fourier transform infrared spectra, X-ray diffraction and differential scanning calorimetry of ibuprofen solid dispersions and artesunate solid dispersions showed the molecularly miscible state of the drugs and the hydrogen bonding between the drugs and polyvinyl pyrrolidone. The NVP-based solid dispersions of the two drugs had faster and more complete dissolution than their traditional solid dispersions. The NVP photopolymerization-based solid dispersion method provides a new choice for the production of solid dispersions in the research and industrial fields.

布洛芬固体分散体的制备及其物相鉴别研究

布洛芬固体分散体的制备及其物相鉴别研究

Applying Supercritical Fluid Technology to Prepare Ibuprofen Solid Dispersions with Improved Oral Bioavailability.

In this study, supercritical fluid (SCF) technology was applied to prepare reliable solid dispersions of pharmaceutical compounds with limited bioavailability using ibuprofen (IBU) as a model compound. Solid-state characterization of the dispersions was conducted by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The PXRD and DSC results suggested that the amorphous form of IBU was maintained in the solid dispersions. Furthermore, in vitro dissolution and in vivo pharmacokinetic (PK) studies in rats were also performed. The dissolution performance of the SCF-prepared IBU dispersions was significantly improved compared to that of the physical mixtures of crystalline IBU and a polymer. In addition, the PK results revealed that the SCF-prepared IBU dispersions produced remarkably high blood drug concentrations (both the AUC and Cmax) and a rapid absorption rate (Tmax). Finally, molecular modeling was used to evaluate the binding energy of interactions between IBU and the polymers. The negative binding energy suggests a relatively stable system. Hence, SCF technology can be used as a very effective approach to prepare IBU solid dispersions with good physical stability and enhanced in vitro and in vivo performance.

Impact Assessment of Different Polymers on Physicochemical Properties of Ibuprofen Loaded Solid Dispersions

In the present study, solid dispersions of ibuprofen were prepared to improve aqueous solubility of ibuprofen. A series of formulations were prepared where PEG 6000 with polymers named PVP K30, cross PVP, poloxamer 237, HPMC ASLF, pregelatinized starch, Na-CMC, Eudragit L100, and kollidon IR were used in different ratios. Among 41 formulations, solid dispersions of ibuprofen in PEG 6000 with each of PVP K30, poloxamer 237, and Na-CMC at ratio of 2:9:7 revealed improved solubility of 952.73 ± 1.31, 878.18 ± 0.97, and 1263.64 ± 1.58 μg/ml, respectively. The physicochemical properties of these preparations were ascertained by FTIR, SEM, DSC, and particle size analyses. FTIR spectrum showed absence of chemical interactions and physical compatibilities between ibuprofen and polymers were confirmed by DSC. Disappearance of individual surface properties in solid dispersions were revealed by SEM studies, which indicated the formation of effective preparations. On the other hand, particle size analysis showed reduction in particle size of ibuprofen from solid dispersions that demonstrated solubility enhancement of ibuprofen. The above studies suggested that solid dispersions of ibuprofen in PEG 6000 at ratios of 2:9:7 with each of PVP K30, poloxamer 237, and Na-CMC were found to be effective to improve aqueous solubility.&#x0D; Dhaka Univ. J. Pharm. Sci. 17(2): 183-190, 2018 (December)

Preparation and Evaluationof Ibuprofen Solid Dispersion Tablets with Improved Dissolution and Less Sticking Using Porous Calcium Silicate

Preparation and Evaluationof Ibuprofen Solid Dispersion Tablets with Improved Dissolution and Less Sticking Using Porous Calcium Silicate

ENHANCEMENT OF SOLUBILITY AND DISSOLUTION OF IBUPROFEN BY SOLID DISPERSION TECHNIQUE AND FORMULATION OF SUSTAINED RELEASE TABLETS CONTAINING THE OPTIMISED BATCH OF SOLID DISPERSION

Objective: The present study was aimed to enhance the solubility of poorly water soluble drug Ibuprofen using solid dispersion technique and to develop sustained release tablets containing solid dispersion granules of the optimized batch. Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) with analgesic, antipyretic, and anti-inflammatory propertiesMethods: Solid dispersions of Ibuprofen were prepared by using PEG 20000 and Poloxamer 407 in different weight ratios by fusion and solvent evaporation method. Drug-carrier physical mixtures were also prepared. Solid dispersions were characterized by saturation solubility, drug content, in vitro dissolution, FTIR and DSC analysis. Solid dispersion formulation, SDF9 (PEG 20000 and Poloxamer 407, 1:3:3) prepared by solvent evaporation method was considered as the optimized batch. Sustained release tablets containing the solid dispersion granules of the optimized batch were prepared by direct compression method using HPMC K100M at three concentrations (10%, 14%, 18% w/w). The prepared formulations were evaluated for hardness, thickness, weight variation, friability, in vitro dissolution studies and release kinetics modelling.Results: Solid dispersion formulation, SDF9showed 95.09% drug release in 60 min and considered as the optimized batch. Tablet formulation, FT3 (HPMC K100M 18% w/w) showed 96% drug release for 12 h.Conclusion: Solid dispersions of ibuprofen using a combination of PEG 20000 and poloxamer 407 by solvent evaporation method may result in higher aqueous solubility of the drug. Also sustained release tablets containing solid dispersion granules of ibuprofen, using HPMC K100M may be a promising approach to extend the release rate of the drug from the solid dispersion for 12 h.

Mathematical model to analyze the dissolution behavior of metastable crystals or amorphous drug accompanied with a solid-liquid interface reaction

Metastable crystals and the amorphous state of poorly water-soluble drugs in solid dispersions (SDs), are subject to a solid-liquid interface reaction upon exposure to a solvent. The dissolution behavior during the solid-liquid interface reaction often shows that the concentration of drugs is supersaturated, with a high initial drug concentration compared with the solubility of stable crystals but finally approaching the latter solubility with time. However, a method for measuring the precipitation rate of stable crystals and/or the potential solubility of metastable crystals or amorphous drugs has not been established. In this study, a novel mathematical model that can represent the dissolution behavior of the solid-liquid interface reaction for metastable crystals or amorphous drug was developed and its validity was evaluated. The theory for this model was based on the Noyes-Whitney equation and assumes that the precipitation of stable crystals at the solid-liquid interface occurs through a first-order reaction. Moreover, two models were developed, one assuming that the surface area of the drug remains constant because of the presence of excess drug in the bulk and the other that the surface area changes in time-dependency because of agglomeration of the drug. SDs of Ibuprofen (IB)/polyvinylpyrrolidone (PVP) were prepared and their dissolution behaviors under non-sink conditions were fitted by the models to evaluate improvements in solubility. The model assuming time-dependent surface area showed good agreement with experimental values. Furthermore, by applying the model to the dissolution profile, parameters such as the precipitation rate and the potential solubility of the amorphous drug were successfully calculated. In addition, it was shown that the improvement in solubility with supersaturation was able to be evaluated quantitatively using this model. Therefore, this mathematical model would be a useful tool to quantitatively determine the supersaturation concentration of a metastable drug from solid dispersions.

Development of a binary carrier system consisting polyethylene glycol 4000 - ethyl cellulose for ibuprofen solid dispersion.

Background and Objective:One of the established strategies to improve solubility and dissolution rate of poorly water-soluble drugs is solid dispersion (SD). Polyethylene glycol (PEG) is used as common carrier despite its stability problem which may be overcome by the addition of hydrophobic polymer. The present research aimed to develop an SD formulation with ibuprofen, a poor water-soluble BCS Class II drug as active pharmaceutical ingredient (API) and PEG 4000-ethyl cellulose (EC) as binary carrier.Methods:Melt mixing SD method was employed using a ratio of API: binary carrier (1:3.5 w/w) (SDPE). Another SD was prepared using only PEG (SDP) as a carrier for comparative study. The developed formulation was evaluated using optical microscopy, scanning electron microscopy (SEM), determination of moisture content, differential scanning calorimetry (DSC), in vitro dissolution test, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and flow properties.Results:SEM and DSC indicated the conversion of crystalline ibuprofen to fine partly amorphous solid dispersion, which was responsible for the increase in dissolution rate of SD than a physical mixture. The release characteristics within 1 h from the higher to the lower value were the SDPE> SDP> physical mixture. Flow property evaluation using the angle of repose showed no difference between SD and PM. However, by Carr index and Hausner ratio, the flow properties of SDPE was excellent.Conclusion:The SD formulation with the PEG 4000-EC carrier can be effective to enhance in vitro dissolution of ibuprofen immediate release dosage form.

On the inherent properties of Soluplus and its application in ibuprofen solid dispersions generated by microwave-quench cooling technology

Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, or Soluplus®, is a relatively new copolymer and a promising carrier of amorphous solid dispersions. Knowledge on the inherent properties of Soluplus® (e.g. cloud points, critical micelle concentrations, and viscosity) in different conditions is relatively inadequate, and the application characteristics of Soluplus®-based solid dispersions made by microwave methods still need to be clarified. In the present investigation, the inherent properties of a Soluplus® carrier, including cloud points, critical micelle concentrations, and viscosity, were explored in different media and in altered conditions. Ibuprofen, a BCS class II non-steroidal anti-inflammatory drug, was selected to develop Soluplus®-based amorphous solid dispersions using the microwave-quench cooling (MQC) method. Scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Raman spectroscopy (RS), and Fourier transform infrared spectroscopy (FT-IR) were adopted to analyze amorphous properties and molecular interactions in ibuprofen/Soluplus® amorphous solid dispersions generated by MQC. Dissolution, dissolution extension, phase solubility, equilibrium solubility, and supersaturated crystallization inhibiting experiments were performed to elucidate the effects of Soluplus® on ibuprofen in solid dispersions. This research provides valuable information on the inherent properties of Soluplus® and presents a basic understanding of Soluplus® as a carrier of amorphous solid dispersions.

In Vitro Evaluation of Different Approaches and Dissolution Enhancement Technique of Poorly Water-Soluble Drug Ibuprofen

Ibuprofen Solid Dispersion (SD) was prepared by simple Physical Mixing (PM) and Kneading Method (KM). In these two cases, four polymers named poloxamer 407, sodium carboxy methyl cellulose, croscarmellose sodium and pregelatinized starch were used to enhance the dissolution profile of Ibuprofen. In both methods, the ratio of drug and carrier were 1:1, 1:2, 1:3 of which the ratio of 1:3 in KM gave comparatively better result than PM method. In vitro dissolution study was performed in distilled water in 50 rpm and at 37 ± 0.5°C. In case of pure Ibuprofen, dissolution rate was only 26% after 60 minutes (mins) of dissolution. While in KM, Ibuprofen pregelatinized starch formulation at 1:3 ratio showed better dissolution rate. After 60 mins, dissolution rate of Ibuprofen was 72%. The SD formulations of Ibuprofen-pregelatinized starch and Ibuprofen-Na-CMC of physical mixing and kneading techniques (1:3 ratio) were characterized by Fourier Transform Infrared Spectroscopy (FTIR).&#x0D; Dhaka Univ. J. Sci. 64(2): 169-175, 2016 (July)

TRANSDERMAL PERMEATION ENHANCEMENT OF IBUPROFEN AND ITS SOLID DISPERSIONS

Terpenes are the most promising natural chemical enhancers used to amplify the transdermal permeation of drugs, among them mo noterpenes and sesquiterpenes have been widely suggested. Permeation enhancement effect of various terpenes (nerolidol, farnesol, limonene, linalool, menthol, geraniol, carvone, fenchone etc.) in various combinations of preparations on ibuprofen (IBU) and its solid dispersions (IBUSD 1 ) from Carbopol 941 gel formulations (0.9 %) were studied. Skin permeation studies and release kinetics have shown farnesol (2.5 and 5 %) and geraniol (2.5 %) had the best permeation enhancement on the release rate of ibuprofen gel. Limonene (2.5 %), gerani ol (2.5 and 5 %) had the best permeation enhancement on the release rate of ibuprofen solid dispersion gel. Ex - vivo studies of ibuprofen gel revealed that farnesol with highest lipophilicity (log P 5.31) significantly (p geraniol (230 o C) and that of ibuprofen solid dispersion gel was limonene (176 o C) > geraniol (230 o C). A ll optimized formulations obeyed the Higuchi release kinetics and non

Preparation and Evaluation of Solid Dispersions of Ibuprofen Using Glucosamine HCl as a Carrier

Preparation and Evaluation of Solid Dispersions of Ibuprofen Using Glucosamine HCl as a Carrier

Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.

Ibuprofen–phospholipid solid dispersions: Improved dissolution and gastric tolerance

Solid dispersions of ibuprofen with various phospholipids were prepared, and the effect of phospholipids on the in vitro dissolution and in vivo gastrointestinal toxicity of ibuprofen was evaluated. Most phospholipids improved the dissolution of ibuprofen; dimyristoylphosphatidyl-glycerol (DMPG) had the greatest effect. At 45 min, the extent of dissolution of ibuprofen from the ibuprofen–DMPG system (weight ratio 9:1) increased about 69% compared to ibuprofen alone; the initial rate of dissolution increased sevenfold. Increasing the DMPG content from 9:1 to 4:1 in this system did not significantly increase the rate and the extent of dissolution. X-ray diffraction and scanning electron micrograph indicated a smaller crystallite size of ibuprofen with fairly uniform distribution in the ibuprofen–DMPG solid dispersion. A small amount of carrier phospholipid significantly increases the rate and the extent of dissolution, which may increase the bioavailability of ibuprofen. The number of ulcers >0.5 mm in size formed in the gastric mucosa of rats following ibuprofen, DMPG, DMPC and DPPC solid dispersions (ibuprofen and phospholipid weight ratio 4:1) were 8.6 ± 6.2, 3.9 ± 5.3, 5.3 ± 4.9 and 9.1 ± 7.4, respectively. Solid dispersion of ibuprofen with DMPG was significantly less irritating to the gastric mucosa than ibuprofen itself (one-way ANOVA, p < 0.05). Solid dispersion of ibuprofen and DMPG decreases the gastric side effects of ibuprofen.

Reciprocal Powered Time model for Release Kinetic Analysis of Ibuprofen Solid Dispersions in Oleaster Powder, Microcrystalline Cellulose and Crospovidone

A physically sound derivation for reciprocal power time (RPT) model for kinetic of drug release is given. In order to enhance ibuprofen dissolution, its solid dispersions (SDs) prepared by cogrinding technique using crospovidone (CP), microcrystalline cellulose (MC) and oleaster powder (OP) as a novel carrier and the model applied to the drug release data. The drug cogrounds with the carriers were prepared and subjected to the dissolution studies. For elucidation of observed in vitro differences, FT-IR spectroscopy, X-ray diffraction patterns, DSC thermograms and laser particle size measurement were conducted. All drug release data fitted very well to newly derived RPT model. The efficiency of the carriers for dissolution enhancement was in the order of: CP>OP>MC. The corresponding release kinetic parameter derived from the model, t50% (time required for 50% dissolution) for the carrier to drug ratio 2:1 were 2.7, 10.2 and 12.6 min, respectively. The efficiency of novel carrier, OP, was between CP and MC. FT-IR showed no interaction between the carriers and drug. The DSC thermograms and X-ray diffraction patterns revealed a slight reduced crystallinty in the SDs. Also grinding reduced mean particle size of drug from 150.7 to 44.4 microm. An improved derivation for RPT model was provided which the parameter of the model, t50%, unlike to previous derivations was related to the most important property of the drug i.e. its solubility. The model described very well drug release kinetics from the solid dispersions. Cogrinding was an effective technique in enhancing dissolution rate of ibuprofen. Elaeagnus angostifolia fruit powder was suggested as a novel potential hydrophilic carrier in preparing solid dispersion of ibuprofen.

Improvement of dissolution rate of ibuprofen by solid dispersion systems with Kollicoat IR using a pulse combustion dryer system

We prepared solid dispersions (SDs) of ibuprofen (IBU) with Kollicoat IR as the carrier using a newly developed pulse combustion dryer system-Hypulcon. We investigated the physicochemical properties of the prepared SDs by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), and Fourier Transform IR spectroscopy (FT-IR). The results showed that the dissolution property of IBU in SDs was markedly enhanced. The dissolution test showed that after 5 min of dissolution, the concentration of IBU in 1:10 SD with Kollicoat IR as the carrier was 23.05 μg/mL, corresponding to 37.8-fold higher than that of pure IBU. The dissolution rate of IBU in SDs was 1:10 SD 49.7-fold higher than that of pure IBU. It can therefore be said that the pulse combustion dryer system is effective for preparing SDs of IBU with Kollicoat IR, a new carrier.