Evaluation of melt granulation and ultrasonic spray congealing as techniques to enhance the dissolution of praziquantel

Praziquantel (PZQ), an anthelminthic drug widely used in developing countries, is classified in Class II in the Biopharmaceutics Classification Systems; this means that PZQ has very low water solubility and high permeability, thus the dissolution is the absorption rate-limiting factor. The aim of this work was to evaluate the suitability of melt granulation and ultrasonic spray congealing as techniques for enhancing the dissolution rate of PZQ. Granules in high shear mixer were prepared by melt granulation, using polyethylene glycol 4000 or poloxamer 188 as meltable binders and alpha-lactose monohydrate as a filler. Quite regularly shaped granules having main size fraction in the range 200-500 microm were obtained using both formulations; however, only poloxamer 188 granules demonstrated a significant (P=0.05) increase of the PZQ dissolution rate compared to pure drug. To evaluate the potential of ultrasonic spray congealing, Gelucire 50/13 microparticles having different drug to carrier ratios (5, 10, 20 and 30%, w/w) were then prepared. The results showed that all the microparticles had a significant higher dissolution rate (P=0.05) respect to pure PZQ. The increase of the PZQ content considerably decreased the dissolution rate of the drug: 5 and 10% PZQ loaded systems evidenced dissolution significantly enhanced compared to 20 and 30% PZQ microparticles. The microparticle's characterisation, performed by Differential Scanning Calorimetry, Hot Stage Microscopy, X-ray powder diffraction and FT-Infrared analysis, evidenced the absence of both modifications of the solid state of PZQ and of significant interactions between the drug and the carrier. In conclusion, melt granulation and ultrasonic spray congealing could be proposed as solvent free, rapid and low expensive manufacturing methods to increase the in vitro dissolution rate of PZQ.     

Characterization of agglomerated carvedilol by hot-melt processes in a fluid bed and high shear granulator

The purpose of this study was to prepare and characterize granulated carvedilol by melt-in and spray-on melt granulation in a fluid bed and a high shear granulator. Granulates having comparable particle size distribution and good flow properties were obtained with proper adjustment of process parameters for each binder (poloxamer 188, polyethylene glycol 4000, and gliceryl monosterate), procedure (spray-on and melt-in) and equipment (fluid bed and high shear granulator). In-line probes for particle size measurements proved to be a useful tool for determining the end point of melt granulation. The product temperature during melt granulation was found to be the critical process parameter for achieving appropriate granulate particle size distribution. The results showed that melt granulation using hydrophilic binders is an effective method to improve the dissolution rate of carvedilol. The method of binder addition to the powders (melt-in or spray-on procedure) was found to strongly influence the dissolution rate of carvedilol. The highest dissolution rates were obtained when the spray-on procedure is used, independently from the type of granulator used. The results also suggest that the most probable explanation for the increase in the dissolution rate of granulated carvedilol is improvement of the wettability through intimate contact between hydrophilic binder and hydrophobic drug.     

Effect of the melt granulation technique on the dissolution characteristics of griseofulvin

This work describes a melt granulation technique to improve the dissolution characteristics of a poorly water-soluble drug, griseofulvin. Melt granulation technique is a process by which pharmaceutical powders are efficiently agglomerated by a meltable binder. The advantage of this technique compared to a conventional granulation is that no water or organic solvents is needed. Because there is no drying step, the process is less time consuming and uses less energy than wet granulation. Granules were prepared in a lab scale high shear mixer, using a jacket temperature of 60 degrees C and an impeller speed of approximately 20,000 rpm. The effect of drug loading (2.5/5%), binder (PEG 3350/Gelucire 44/14), filler (starch/lactose), and HPMC on the dissolution of griseofulvin was investigated using a half two level-four factor factorial design. The granules were characterized using powder XRD, DSC and SEM techniques. A significant enhancement in the in vitro dissolution profiles of the granules was observed compared to the pure drug and drug excipient physical mixtures. The factorial design results indicated that higher drug loading and the presence of HPMC reduced the extent of dissolution of the drug, whereas, the presence of starch enhanced the dissolution rate. XRD data confirmed crystalline drug in formulation matrices. DSC results indicated monotectic mixtures of griseofulvin with PEG in the granulated formulations. In conclusion, the results of this work suggest that melt granulation is a useful technique to enhance the dissolution rate of poorly water-soluble drugs, such as, griseofulvin.     

Effect of a melt agglomeration process on agglomerates containing solid dispersions

The purpose was to produce solid dispersions of a poorly water-soluble drug, Lu-X, by melt agglomeration in a laboratory scale rotary processor. The effect of binder type and method of manufacturing on the dissolution profile of Lu-X was investigated. Lactose monohydrate and Lu-X were melt agglomerated with Rylo MG12, Gelucire 50/13, PEG 3000, or poloxamer 188. Either a mixture of binder, drug, and excipient was heated to a temperature above the melting point of the binder (melt-in procedure) or a dispersion of drug in molten binder was sprayed on the heated excipient (spray-on procedure). The agglomerates were characterized by DSC, XRPD, SEM, and EDX-SEM. The study showed that the agglomerates containing solid dispersions had improved dissolution rates compared to physical mixtures and pure drug. The melt-in procedure gave a higher dissolution rate than the spray-on procedure with PEG 3000, poloxamer 188, and Gelucire 50/13, whereas the opposite was found with Rylo MG12. This was explained by differences in mechanisms of agglomerate formation and growth, which were dominated by immersion with PEG 3000, poloxamer 188, and Gelucire 50/13, and by distribution and coalescence with Rylo MG12. The spray-on procedure resulted in a higher content of Lu-X in the core of the agglomerates when immersion was the dominating mechanism, and in a higher content in the agglomerate surface when distribution was dominating. The melt-in procedure resulted generally in a homogeneous distribution of Lu-X in the agglomerates. The compounds in the agglomerates were found primarily to be crystalline, and the dissolution profiles were unchanged after 12 weeks storage at 25 degrees C at 50% RH.     

An investigation into the effect of formulation variables and process parameters on characteristics of granules obtained by in situ fluidized hot melt granulation

The aim of this study was to investigate the influence of binder content, binder particle size, granulation time and inlet air flow rate on granule size and size distribution, granule shape and flowability, as well as on drug release rate. Hydrophilic (polyetilenglycol 2000) and hydrophobic meltable binder (glyceryl palmitostearate) were used for in situ fluidized hot melt granulation. Granule size was mainly influenced by binder particle size. Binder content was shown to be important for narrow size distribution and good flow properties. The results obtained indicate that conventional fluid bed granulator may be suitable for production of highly spherical agglomerates, particularly when immersion and layering is dominant agglomeration mechanism. Granule shape was affected by interplay of binder content, binder particle size and granulation time. Solid state analysis confirmed unaltered physical state of the granulate components and the absence of interactions between the active and excipients. Besides the nature and amount of binder, the mechanism of agglomerate formation seems to have an impact on drug dissolution rate. The results of the present study indicate that fluidized hot melt granulation is a promising powder agglomeration technique for spherical granules production.     

Improved solubility and in vitro dissolution of Ibuprofen from poloxamer gel using eutectic mixture with menthol

To improve the solubility and in vitro dissolution of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution study of ibuprofen delivered by poloxamer gels composed of poloxamer 188 and menthol were performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6, followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that 4 parts of ibuprofen formed eutectic mixture with 6 parts of menthol. In the presence of poloxamer 188, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without poloxamer and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Dissolution mechanism showed that the dissolution rate of ibuprofen from the poloxamer gels without menthol was independent of the time, but the drug might be dissolved from the poloxamer gels with menthol by Fickian diffusion. Thus, the poloxamer gels developed using eutectic mixture with menthol, which gave the improved solubility and dissolution of drug, are potential candidates for ibuprofen-loaded transdermal and rectal delivery system.     

Enhanced rectal bioavailability of ibuprofen in rats by poloxamer 188 and menthol

To improve the bioavailability of poorly water-soluble ibuprofen in the rectum with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the poloxamer gels composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Release mechanism showed that the release rate of ibuprofen from the poloxamer gels without menthol was independent of the time but the drug might be released from the poloxamer gels with menthol by Fickian diffusion. Furthermore, the poloxamer gel with menthol (poloxamer/menthol/ibuprofen (15%/0.25%/2.5%)) gave significantly higher initial plasma concentrations, C(max) and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the poloxamer gel with poloxamer 188 and menthol was a more effective rectal dosage form for ibuprofen.     

Drug-fatty acid salt with wax-like properties employed as binder in melt granulation

The tacky and deformable properties of a wax-like drug-fatty acid salt, propranolol oleate (POA), make particle size reduction and separation challenging. The aim of this study was to investigate the use of POA as binder in a melt granulation procedure to improve processing properties. POA is a suitable candidate for binder phase in melt granulation with a melting temperature of 50-56 degrees C. Small batches (ca 30 g) were manufactured using a high shear mixer with lactose monohydrate as the substrate phase. Optimum uniformity of drug content and minimum friability were found at 10% w/w POA binder concentration. POA melt granules exhibited a >10-fold increase in the rate of in vitro dissolution at pH 7.4 with 0.2% w/v sodium lauryl sulphate compared with raw POA. The increased drug surface area in granular form was thought to be responsible for the change in dissolution behaviour. This study has demonstrated that melt granulation using POA as binder is a viable process which leads to beneficial changes in dissolution behaviour for the lipophilic drug-fatty acid salt.     

Effect of formulation and processing variables on the granulation kinetics of hot melt granulation (HMG) process

The objective of the study was to evaluate the effect of formulation factors, such as type of drug and particulate properties of a drug, and processing variables, i.e. jacket temperature, impeller speed, and scale, on granulation kinetics the of hot-melt granulation (HMG) process. Two model active pharmaceutical ingredients (API) Ro-A and indomethacin were selected for this evaluation using poloxamer 188 as a meltable binder. The effect of solid-state properties of API was investigated for Ro-A, whereas the binder properties were maintained constant. General factorial design was used to investigate the effect of independent process variables, impeller speed and jacket temperature using impeller motor power consumption as response variable. Consistent granulation could be developed for Ro-A by optimizing the binder level and impeller speed, however, the addition of third excipient was necessary for indomethacin. The granulation rate was related to the bulk density and the surface area of the drug. The jacket temperature affected overall granulation time but had no significant effect on the granulation kinetics, suggesting that faster heating rate is desirable for optimal productivity. A significant increase in the granulation rate was observed with increase in impeller speed. The effect of impeller speed was further confirmed at 5 L and 25 L scale. From the formulation prospective, the critical factors were the level of binder, inherent binding properties of the API, the solid-state properties of API and binder. From processing perspectives, the impeller speed had a significant effect on the granulation kinetics.     

Effect of Formulation and Processing Variables on the Granulation Kinetics of Hot Melt Granulation (HMG) Process

The objective of the study was to evaluate the effect of formulation factors, such as type of drug and particulate properties of a drug, and processing variables, i.e. jacket temperature, impeller speed, and scale, on granulation kinetics the of hot-melt granulation (HMG) process. Two model active pharmaceutical ingredients (API) Ro-A and indomethacin were selected for this evaluation using poloxamer 188 as a meltable binder. The effect of solid-state properties of API was investigated for Ro-A, whereas the binder properties were maintained constant. General factorial design was used to investigate the effect of independent process variables, impeller speed and jacket temperature using impeller motor power consumption as response variable. Consistent granulation could be developed for Ro-A by optimizing the binder level and impeller speed, however, the addition of third excipient was necessary for indomethacin. The granulation rate was related to the bulk density and the surface area of the drug. The jacket temperature affected overall granulation time but had no significant effect on the granulation kinetics, suggesting that faster heating rate is desirable for optimal productivity. A significant increase in the granulation rate was observed with increase in impeller speed. The effect of impeller speed was further confirmed at 5 L and 25 L scale. From the formulation prospective, the critical factors were the level of binder, inherent binding properties of the API, the solid-state properties of API and binder. From processing perspectives, the impeller speed had a significant effect on the granulation kinetics.     

The preparation of agglomerates containing solid dispersions of diazepam by melt agglomeration in a high shear mixer

The aim of this study was to prepare by melt agglomeration agglomerates containing solid dispersions of diazepam as poorly water-soluble model drug in order to evaluate the possibility of improving the dissolution rate. Lactose monohydrate was melt agglomerated with polyethylene glycol (PEG) 3000 or Gelucire 50/13 (mixture of glycerides and PEG esters of fatty acids) as meltable binders in a high shear mixer. The binders were added either as a mixture of melted binder and diazepam by a pump-on procedure or by a melt-in procedure of solid binder particles. Different drug concentrations, maximum manufacturing temperatures, and cooling rates were investigated. It was found to be possible to increase the dissolution rate of diazepam by melt agglomeration. A higher dissolution rate was obtained with a lower drug concentration. Admixing the binders by the melt-in procedure resulted in similar dissolution rates as the pump-on procedure. The different maximum manufacturing temperatures and cooling rates were found to have complex effects on the dissolution rate for formulations containing PEG 3000, whereas only minor effects of the cooling procedure were found with Gelucire 50/13. Gelucire 50/13 resulted in faster dissolution rates compared to PEG 3000.     

盐酸小檗碱泊洛沙姆188固体分散体的制备

目的:制备盐酸小檗碱泊洛沙姆188固体分散体。方法:采用熔融法制备固体分散体,考察药物和载体的比例、熔融温度、冷却温度对溶出率的影响,比较固体分散体和物理混合物的溶出率的区别。结果:药物和载体比例达到1∶1时,载体的量足够使药物分散均匀;熔融温度对溶出率影响不大;冷却温度对溶出率影响较大,0℃时溶出率最快。与物理混合物相比,固体分散体将盐酸小檗碱的溶出率提高了近1倍。结论:盐酸小檗碱泊洛沙姆188固体分散体提高了盐酸小檗碱的体外溶出率。     

Preparation and characterization by morphological analysis of diclofenac/PEG 4000 granules obtained using three different techniques

The steam granulation is a new wet granulation technique, which involves the use of steam water instead of traditional liquid water as granulation liquid. The aim of this work was to evaluate the possibility of using this new technique to prepare diclofenac-polyethylene glycol 4000 accelerated-release granules. Steam granules were prepared in a laboratory scale high-shear mixer, and their properties were then compared to those of granules, having the same composition, obtained by traditional granulation techniques (wet and melt granulation). The results showed that, selecting the proper process parameters, it was possible to obtain granules using all the three methods; however, the total process time was significantly shorter for steam granulation (30 min) in comparison to traditional wet granulation (70 min), due to the lower amount of used water. The morphological characterization of steam, water and melt granules, performed by scanning electron microscopy (SEM) and image analysis, revealed that steam granules had a more spherical shape and a larger surface area with respect to water and melt ones, suggesting a possible difference in dissolution behavior. Moreover, differential scanning calorimetry (DSC) and X-ray powder diffraction analysis evidenced the transformation of the drug from its originally crystalline form into the amorphous one. Finally, the in vitro dissolution tests showed an increased dissolution rate of the drug from the granules (in particular steam granules) in comparison to pure drug and physical mixture. In conclusion, the results of this study suggested that the steam granulation technique could be considered an interesting alternative to traditional wet granulation to improve the dissolution rate of diclofenac.     

Formulation design of carbamazepine fast-release tablets prepared by melt granulation technique

This work describes a new approach to prepare a fast-release dosage form for carbamazepine (CBZ), involving the use of melt granulation process in high shear mixer for the production of tablets. In particular, the granules containing CBZ were prepared using polyethylene glycol (PEG) 4000 as a melting binder and lactose monohydrate as a hydrophilic filler. The potential of the intragranular addition of crospovidone as a dissolution enhancer and a disintegrant agent was also evaluated. After the analysis of their solid state performed by means of X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC), the granules were characterised from the technological and dissolution point of view. The subsequent step encompassed the preparation and the evaluation of the tablets, including the effect of the extragranular introduction of crospovidone. Besides the remarkable enhancement of drug dissolution rate of the granulates in comparison to physical mixtures and pure drug, no significant differences were found between the dissolution profiles of the granulates containing lactose or crospovidone. However, the difficult disintegration and bad dissolution performance of the tablets not containing intragranular crospovidone highlight the necessity of this disintegrant in the granulating mixture. Moreover, the extragranular addition of a small amount of crospovidone gave rise to a further amelioration of the disintegration and dissolution performances.     

Preparation and physicochemical characterizations of tanshinone IIA solid dispersion

This investigation describes a novel approach to prepare solid dispersions of tanshinone IIA using a laboratory-scale planetary ball mill. Poloxamer 188 was employed as the surfactant carrier to improve the solubility and dissolution of the poorly soluble drug, tanshinone IIA. Solubility and dissolution were evaluated compared to the corresponding physical mixtures and pure drug. Furthermore, the physicochemical properties of the solid dispersions were investigated using scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and ultraviolet spectrophotometry. The solid dispersion significantly enhanced drug solubility and dissolution compared with pure drug and the physical mixtures. Scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry and Fourier transform infrared spectroscopy analyses of tanshinone IIA/poloxamer 188 system confirmed that there were intermolecular interactions between tanshinone IIA and poloxamer 188 and no conversion to crystalline material. Tanshinone IIA existed in a microcrystalline form in the system. These results suggested that improvement of the dissolution rate could be correlated to the formation of a eutectic mixture between the drug and the carrier. After 60 days the solid dispersion samples were chemically and physically stable. The present studies indicated that the planetary ball mill technique could be considered as a novel and efficient method to prepare solid dispersion formulations.     

Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol

To prepare an ibuprofen-loaded liquid suppository using eutectic mixture with menthol, the effects of menthol and poloxamer 188 (P 188) on the aqueous solubility of ibuprofen were investigated. The physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of ibuprofen, menthol and P 188 were investigated. Then, the pharmacokinetic study of ibuprofen delivered by the liquid suppositories composed of P 188 and menthol were then performed. In the absence of P 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts of ibuprofen formed eutectic mixture with six parts of menthol. In the presence of P 188, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Ibuprofen increased the gelation temperature and weakened the gel strength and bioadhesive force of liquid suppositories. However, menthol did the opposite due to forming the eutectic mixture with ibuprofen. The ibuprofen-loaded liquid suppository [P 188/menthol/ibuprofen (15/0.25/2.5%)] with the maximum ibuprofen solubility of 1.2mg/ml was administered easily to the anus and to remain at the administered site without leakage after the dose. Furthermore, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the liquid suppository system with P 188 and menthol, a more convenient and effective rectal dosage form for ibuprofen will be expected to enhance the rectal bioavailability of ibuprofen.     

The preparation of orally disintegrating tablets using a hydrophilic waxy binder

The demand for rapidly disintegrating tablets (RDT) has been growing during the last decade especially for elderly and children who have swallowing difficulties. The problem of certain RDT is their low physical resistance and high friability. This work describes a new approach to prepare RDT with sufficient mechanical integrity, involving the use of a hydrophilic waxy binder (Superpolystate, PEG-6-stearate). Superpolystate is a waxy material with a melting point of 33-37 degrees C and an HLB value of 9. So it will not only act as a binder and increase the physical resistance of tablets but will also help the disintegration of the tablets as it melts in the mouth and solublises rapidly leaving no residues. The incorporation of Superpolystate in the formulation of RDT was realised by means of two different granulation methods: wet granulation by using an emulsion of this waxy binder as granulating liquid and melt granulation where the molten form of the binder was used. Granule size distributions of both wet and melt granules of crystallised Paracetamol and D-mannitol were compared using laser light diffractometer. Scanning electron microscopy (SEM) was used to examine their morphological characteristics. The potential of the intragranular addition of croscarmellose sodium as a disintegrating agent was also evaluated. The subsequent step encompassed the preparation and the evaluation of the tablets, including the effect of the extragranular introduction of croscarmellose sodium. An improvement in tablet hardness and friability was observed with both granulation methods where we were able to obtain RDT with a disintegration time of 40 +/- 2 s and a hardness of 47.9 +/- 2.5N.     

Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting point of various formulations composed of poloxamer 124 (P 124) and poloxamer 188 (P 188) were investigated. The dissolution and pharmacokinetic study of diclofenac sodium delivered by the poloxamer-based suppository were performed. Furthermore, the identification test in the rectum and morphology test of rectal tissues were carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous phases. Very small amounts of P 188 affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32 degrees C was a solid form at room temperature and instantly melted at physiological temperature. Very small amounts of P 188 hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. The poloxamer-based suppository gave significantly higher initial plasma concentrations and faster T(max) of diclofenac sodium than did conventional PEG-based suppository, indicating that the drug from poloxamer-based suppository could be absorbed faster than that from PEG-based one in rats. It retained in the rectum for at least 4 h and could not irritate or damage the rectal tissues of rats. Thus, the poloxamer-based solid suppository with P 124 and P 188 was a mucoadhesive, safe and effective rectal dosage form for diclofenac sodium.     

Enhanced dissolution of ibuprofen using solid dispersion with poloxamer 407

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility, and in-vitro ibuprofen release. Loss of individual surface properties during melting and re-solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. FTIR spectra showed the presence of drug crystalline in SDs. The effect of improved dissolution on the oral absorption of ibuprofen in rats was also studied. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C_max, and a significant decrease in T_max over pure ibuprofen. Comparison of the enhanced solubility, dissolution, AUC, and C_max of ibuprofen from different poloxamers suggested that the preparation of ibuprofen SDs using P 407 as a meltable hydrophilic polymer carrier could be a promising approach to improve its solubility, dissolution and absorption rate.     

Preparation and evaluation of immediate release ibuprofen solid dispersions using polyethylene glycol 4000

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), and evaluated for solubility, in-vitro drug release and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and resolidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. FT-IR spectra showed the presence of drug crystalline in SDs. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and Cmax, and a significant decrease in Tmax over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low temperature melting method using polyethylene glycol 4000 (PEG 4000) as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution and absorption rate of ibuprofen.