Pure Carbamazepine Research Articles

Fabrication of Carbamazepine Cocrystals: Characterization, In Vitro and Comparative In Vivo Evaluation.

Carbamazepine (CBZ) is an antiepileptic drug having low bioavailability due to its hydrophobic nature. In the current study, efforts are made to investigate the effect of dicarboxylic acid coformer spacer groups (aliphatic chain length) on physicochemical properties, relative humidity (RH) stability, and oral bioavailability of CBZ cocrystals. Slurry crystallization technique was employed for the preparation of CBZ cocrystals with the following coformers: adipic (AA), glutaric (GA), succinic (SA), and malonic acid (MA). Powder X-ray diffractometry and Fourier-transform infrared spectroscopy confirmed cocrystal preparation. Physicochemical properties, RH stability, and oral bioavailability of cocrystals were investigated. Among the prepared cocrystals, CBZ-GA showed maximum solubility as well as improved dissolution profile (CBZ-GA > CBZ-MA > CBZ-AA > pure CBZ > CBZ-SA) in ethanol. Maximum RH stability was shown by CBZ-AA, CBZ-SA, and CBZ-MA. In vivo studies confirmed boosted oral bioavailability of cocrystals compared to pure CBZ. Furthermore, in vivo studies depicted the oral bioavailability order of cocrystals as CBZ-GA > CBZ-MA > Tegral® > CBZ-AA > CBZ-SA > pure CBZ. Thus, pharmaceutical scientists can effectively employ cocrystallization technique for tuning physicochemical properties of hydrophobic drugs to achieve the desired oral bioavailability. Overall, results reflect no consistent effect of spacer group on physicochemical properties, RH stability, and oral bioavailability of cocrystals.

High temperature polymorphic conversion of carbamazepine in supercritical CO2: A way to obtain pure polymorph I

In this work, we studied the high-temperature polymorphic conversion of carbamazepine (CBZ) in a high-density supercritical CO2 (scCO2) medium in the temperature range of 110–200°C. In order to understand the mechanism of transformation we performed a detailed IR analysis of the supercritical fluid (SCF) phase being in permanent contact with an excess of CBZ. We studied the conformational equilibrium of CBZ molecules in scCO2 phase under isochoric heating conditions. Three temperature ranges, where different types of CBZ–scCO2 equilibria are realized, were considered: i. «CBZ solid – SCF solution»; ii. phase transition region related to the melting of CBZ in high-density scCO2; iii. «CBZ melt – SCF solution». An analysis of the IR spectroscopy data on CBZ dissolved in the scCO2 phase obtained for the third temperature range shows that when «CBZ melt – SCF solution» equilibrium exists, the scCO2 phase contains only one CBZ conformer. Relying on this finding, we hypothesized that it is possible to obtain pure CBZ polymorph I by the crystallization from CBZ solution in scCO2. This statement has been proven by the micro-Raman analysis of the crystalline substance being obtained from such fluid solution.

Solubility and Dissolution Improvement of Carbamazepine by Various Methods

This work was aimed to improve solubility and dissolution rate of carbamazepine (CBZ), an antiepileptic, BCS class II drug by using different solubility enhancement techniques. Self-nanoemulsifying drug delivery system (SNEDDS) and solid dispersions of CBZ was attempted by spontaneous emulsification method and fusion method, respectively. The solubility studies of pure CBZ was performed in different oils, surfactants and co-surfactants. Very small amount of CBZ (20 mg) could be incorporated in SNEDDS, however the solid dispersion of CBZ using Soluplus® was successfully prepared with the required dose. The solid dispersion was characterized and evaluated for saturation solubility, in vitro dissolution studies, solid state characterization such as fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction studies (XRD). Based on the results, it can be concluded that the due to increased solubility and the dissolution, the bioavailability of CBZ could be improved by preparing solid dispersion

Transformation Products of Carbamazepine (CBZ) After Ozonation and their Toxicity Evaluation Using Pseudomonas sp. Strain KSH-1 in Aqueous Matrices.

Carbamazepine (CBZ) is an anti-epileptic and anti-convulsant drug widely used for the treatment of epilepsy and other bipolar disorders. Ozone as an advanced oxidation process has been widely used for the degradation of CBZ resulting in the formation of transformation products (ozonides). The present research aims to isolate and identify potential microorganism, capable of degradation of CBZ and its transformation products. The cell viability and cytotoxicity of pure CBZ and their ozone transformation products were evaluated using the cells of Pseudomonas sp. strain KSH-1 through cell viability assay tests. The cells metabolic activity was assessed at varying CBZ concentrations (~ 10-25ppm, pure CBZ) and cumulatively for ozone transformation products. For pure CBZ, % cell viability decreases as CBZ concentration increases, while, in case of post-ozonated CBZ transformation products, the viability decreases initially and then increases upon exposure of ozone with a maximum cell viability of 97 ± 2.8% evaluated for 2h post-ozonated samples.

Polymorphism in the co-crystallization of the anticonvulsant drug carbamazepine and saccharin using supercritical CO2 as an anti-solvent

1:1 Co-crystals of carbamazepine (CBZ) and saccharin (SAC) were obtained for the first time through the supercritical anti-solvent (SAS) technique based on using supercritical CO2 as anti-solvent. The capability of SAS to produce the desired polymorphic form (two polymorphs are known) was assessed. Operational conditions investigated were temperature (40.0 and 60.0 °C), pressure (10.0 and 15.0 MPa), solvent choice and coformer concentration in the organic solution (CBZ: 30 and 15 mg/mL; SAC: stoichiometric ratio). Co-crystals were characterized in terms of crystallinity and coformers interactions. No homocrystals were present. Using methanol, at 40.0 °C polymorph I was obtained with yields up to 65%; whilst at 60.0 °C a mixture of polymorphs was obtained. Mixtures of polymorphs were also obtained in the ethanol and dichloromethane experiments at the studied conditions while the dimethylsulfoxide experiments failed to produce any co-crystal polymorph. For comparison purposes, pure CBZ and SAC were also processed by SAS.

An assessment of triboelectrification effects on co-ground solid dispersions of carbamazepine

One of strategies adopted to improve the dissolution rates of poorly soluble drugs is by co-grinding the drug with a hydrophilic carrier. However, the introduction of mechanical forces during the grinding process can lead to changes in the physicochemical characteristics as well as an increase in the surface free energy of the ground particles, which causes an alteration in the electrostatic properties of these particles. The solid state characteristics of glucosamine hydrochloride (GLU) and carbamazepine (CBZ) and their co-ground mixtures were studied using DSC, XRPD and SEM. These revealed that polymorphic transformations occurred due to the grinding process. The influence of grinding time on the triboelectrification properties of the formulations was also studied. Both pure CBZ and GLU powders were predominantly electro-positively charged and their charging properties increased with increasing grinding time. CBZ:GLU physical mixtures exhibited complicated bipolar charging behaviour, however, when subjected to grinding, these mixtures demonstrated mainly electronegative charge properties. The influence of both grinding time and CBZ content within CBZ:GLU mixtures was examined. The value of net-electronegative-charge density of CBZ:GLU mixtures was shown to increase with grinding time and/or when increasing the percentage proportion of CBZ up to 30% w:w. This study helps to provide information about the handling of these formulations and gives a formulator tools to ascertain appropriate ratios for handling and possible simultaneous dissolution improvements.

Synthesis of bimodal mesoporous carbon spheres from biomass starch and CBZ release

Well-dispersed bimodal mesoporous carbon spheres (BMCSs) with abundant porosity were prepared through a convenient stirring method, in which silica particles were added to improve the porosity of the products. No toxic organic solvent was involved. Thus, the procedure was green and productive. The BMCSs exhibited single or bimodal mesoporous structure, tunable mesopore volume, and specific surface area, which depended on starch concentration. Carbamazepine (CBZ), due to its poor water-solubility and low release rate, was selected as a model drug and loaded onto the as-prepared BMCSs to investigate its release behavior. The experimental results showed that the dissolution rate was significantly increased after CBZ loading onto BMCSs than the pure CBZ, which could be explained by the noncrystalline state, improved dispersibility, and nanoscale size of CBZ in the pore channels of the BMCSs.

Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability.

The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin® UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin® UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine.

Dissolution and solid state behaviours of carbamazepine-gluconolactone solid dispersion powders: The potential use of gluconolactone as dissolution enhancer

Solid dispersions are one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however, this is reliant on the selection of a suitable carrier and solvent. The present study is the mechanistic evaluation of the changes in polymorphic form of carbamazepine when the type of solvent and the concentration of d-gluconolactone (d-GL) change. The studies reported herein also explore the use of d-GL as a potential hydrophilic carrier to improve the dissolution rate of a poorly water-soluble drug, carbamazepine (CBZ), from physical mixtures and solid dispersion formulations. The effect of using different solvents in the preparation of solid dispersion formulations was also investigated. Different ratios of solid dispersions of the drug and d-GL were prepared using a conventional solvent evaporation method. Different solvents (ethanol, acetone and water) were used as a second experimental variable in the preparation of solid dispersions. Physical mixtures of CBZ and d-GL were also prepared for comparison. The results showed that the presence of d-GL can increase the dissolution rate of CBZ compared to pure CBZ. This study showed that d-GL could be used as a new carrier in solid dispersion formulations and physical mixtures. The interesting solid state behaviour of CBZ in all solid dispersions in the presence of d-GL was fully analyzed using Fourier-transform infrared (FT-IR), X-ray powder diffraction (XRPD), scanning electron microscope (SEM), hot stage microscopy (HSM) and differential scanning calorimetry (DSC). The results showed that depending on the type of solvent and concentration of d-GL used in the preparation of solid dispersions different forms of CBZ (Form I, Form III and dihydrate) can be existed in the formulations.

Evaluation of Influence of Various Polymers on Dissolution and Phase Behavior of Carbamazepine-Succinic Acid Cocrystal in Matrix Tablets.

The aim of current study was to explore the influence of three commonly used polymers, that is, cellulosics and noncellulosics, for example, Methocel K4M, Kollidon VA/64, and Soluplus, on the phase disproportionation and drug release profile of carbamazepine-succinic acid (CBZ-SUC) cocrystal at varying drug to polymer ratios (1 : 1 to 1 : 0.25) in matrix tablets. The polymorphic phase disproportionation during in-depth dissolution studies of CBZ-SUC cocrystals and its crystalline properties were scrutinized by X-ray powder diffractrometry and Raman spectroscopy. The percent drug release from HPMC formulations (CSH) showed inverse relation with the concentration of polymer; that is, drug release increased with decrease in polymer concentration. On contrary, direct relation was observed between percent drug release and polymer concentrations of Kollidon VA 64/Soluplus (CSK, CSS). At similar polymer concentration, drug release from pure carbamazepine was slightly lower with HPMC formulations than that of cocrystal; however, opposite trend in release rate was observed with Kollidon VA/64 and Soluplus. The significant increase in dissolution rate of cocrystal occurred with Kollidon VA/64 and Soluplus at higher polymer concentration. Moreover, no phase change took place in Methocel and Kollidon formulations. No tablet residue was left for Soluplus formulation so the impact of polymer on cocrystal integrity cannot be predicted.

Solid self-emulsifying phospholipid suspension (SSEPS) with diatom as a drug carrier

We report the application of diatom as a solid carrier for water insoluble drugs applied in oral drug delivery system based on the self-emulsifying drug delivery system (SEDDS) caprylocaproyl macrogol-8 glycerides/lecithin/propylene glycol/caprylic/capric triglyceride. Diatoms are fossilized skeletons of photosynthetic algae with complex 3-dimensional (3D), porous structure consisting of amorphous silica, obtained by purification of diatomaceous earth. Different solid samples of carbamazepine (CBZ) suspension in SEDDS, called solid self-emulsifying phospholipid suspension (SSEPS), were prepared using two methods: adsorption of CBZ dispersion in SEDDS by gentle mixing with diatoms in mortar with pestle (Method A) or dispersion of diatoms in ethanol solution of CBZ and SEDDS components, followed by ethanol evaporation (Method B). Release rate of CBZ from SSEPS was significantly higher in comparison to pure drug, physical mixture of diatoms and CBZ as well as solid dispersion of pure CBZ and diatoms obtained by ethanol evaporation. The dissolution of CBZ from SSEPS sample prepared using method B was faster than from the sample prepared by the method A. Higher dissolution for sample prepared by the method B can be attributed to the partial adsorption (deeper localization) of liquid material inside the pores of diatoms. Upon storage of the samples under accelerated conditions (40°C and 70% RH) for 10weeks no significant changes in CBZ crystallinity and dissolution was in case of SSEPS, contrary to solid dispersion with increased crystallinity, indicating that diatoms with adsorbed liquid CBZ-loaded SEPS can maintain initial CBZ characteristics.

Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design

This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate. Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate.

Electrochemical characterization and determination of carbamazepine as pharmaceutical standard and tablet content on gold electrode

The anodic behaviour of carbamazepine (CBZ), an anticonvulsant drug, has been studied on gold electrode in 0.1 mol dm-3 phosphate buffer of pH 7.0 by using cyclic voltammetry. It has been found that the value of the oxidative current of pure CBZ at +0.90 V is a linear function of the concentration in a range from 1.0?10-7 to 1.0?10?4 mol dm?3. The detection of CBZ in the concentration of 1.0?10-8 mol dm-3 is among the lowest that have been reported for this drug using voltammetric techniques. CBZ as a content of tablet Galepsine? has been quantitatively determined. It has also been demonstrated that the modification of gold electrode with bovine serum albumin (BSA) results in a decrease of the oxidative peak current due to the binding of the drug to BSA.

Improving the Chemical Stability of Amorphous Solid Dispersion with Cocrystal Technique by Hot Melt Extrusion

To explore in-situ forming cocrystal as a single-step, efficient method to significantly depress the processing temperature and thus minimize the thermal degradation of heat-sensitive drug in preparation of solid dispersions by melting method (MM) and hot melt extrusion (HME). Carbamazepine (CBZ)-nicotinamide (NIC) cocrystal solid dispersions were prepared with polymer carriers PVP/VA, SOLUPLUS and HPMC by MM and/or HME. The formation of cocrystal was investigated by differential scanning calorimetry and hot stage polarized optical microscopy. State of CBZ in solid dispersion was characterized by X-ray powder diffraction and optical microscopy. Interactions between CBZ, NIC and polymers were investigated by FTIR. Dissolution behaviors of solid dispersions were compared with that of pure CBZ. CBZ-NIC cocrystal with melting point of 160°C was formed in polymer carriers during heating process, and the preparation temperature of amorphous CBZ solid dispersion was therefore depressed to 160°C. The dissolution rate of CBZ-NIC cocrystal solid dispersion was significantly increased. By in-situ forming cocrystal, chemically stable amorphous solid dispersions were prepared by MM and HME at a depressed processing temperature. This method provides an attractive opportunity for HME of heat-sensitive drugs.

Sulfobutyl Ether7 β-Cyclodextrin (SBE7 β-CD) Carbamazepine Complex: Preparation, Characterization, Molecular Modeling, and Evaluation of In Vivo Anti-epileptic Activity

The objective of the present investigation was to study the ability of sulfobutyl ether(7)-β-cyclodextrin to form an inclusion complex with carbamazepine, an anti-epileptic drug with poor water solubility. The formation of the complex was carried out using the industrially feasible spray-drying method. The inclusion complex and physical mixtures were characterized by various techniques such as differential scanning calorimetry (DSC), infrared (IR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and molecular modeling. The DSC, IR, and NMR studies confirmed the formation of an inclusion complex between carbamazepine and sulfobutyl ether(7) β-cyclodextrin whereas XRD studies indicated an amorphous nature of the inclusion complex. Molecular modeling studies disclosed different modes of interaction between carbamazepine and sulfobutyl ether(7) β-cyclodextrin with good correlation with experimental observations. The inclusion complex exhibited significantly higher in vitro dissolution profile as compared with pure carbamazepine powder. The in vivo anti-epileptic activity of carbamazepine/sulfobutyl ether(7) β-cyclodextrin complex was evaluated in pentylenetetrazole-induced convulsions model. The carbamazepine/sulfobutyl ether(7) β-cyclodextrin complex showed significantly higher anti-epileptic activity (p <0.01) as compared with that of carbamazepine suspension on oral administration.

Formulation development of Carbamazepine–Nicotinamide co-crystals complexed with γ-cyclodextrin using supercritical fluid process

The objective of the present study was to formulate and characterize co-crystals of Carbamazepine (CBZ) and Nicotinamide (NCT) and inclusion complexes of these co-crystals with γ-cyclodextrin (CD). Gas anti-solvent method of supercritical fluid process (SCF) was used as the method of preparation. Formulations were evaluated by dissolution studies, differential scanning calorimetry, hot stage microscopy, scanning electron microscopy, 1H NMR and X-ray powder diffraction. The dissolution studies show a 2.5-fold increase in dissolution rate in the case of co-crystals and a 40-fold increase when co-crystals were complexed with CD. A lower melting point (160°C) was observed in the case of co-crystals and the exothermic peaks were missing for pure CBZ and co-crystals when they were complexed with CD. The absence of the melting peaks indicates complete complexation. Electron microscopy picture shows the absence of crystallinity in case of inclusion complexes and also the change in crystal structure for CBZ and NCT in the case of co-crystals. X-ray powder diffraction patterns of co-crystals and inclusion complexes were distinct from the starting materials and the shift in peaks of 1H NMR confirmed intermolecular hydrogen bonding and complexation.

Role of humic acid on oral drug delivery of an antiepileptic drug

Context: Humic acid (HA) is omnipresent in natural organic matter that is a macromolecular, negatively charged polyelectrolyte that contains a hydrophobic core. It is also present in a significant amount in Shilajit (used frequently in traditional medicines), which is used in this study as a source of extraction. HA is evaluated for the oral drug delivery of carbamazepine (CBZ). Objective: HA is used in this study to increase the dissolution, intestinal permeation, and pharmacodynamic response of CBZ (bio pharmaceutics classification system (BCS) II) by the technique of complexation and other related mechanism reported with humic substances. Methods: Different complexation techniques were explored in this study for the entrapment of CBZ, which was authenticated by molecular modeling and conformational analysis. These were further characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). Solubility analysis and dissolution release profile were carried out to access the in vitro parameters. For ex vivo studies, rat gut intestinal permeability was done. And finally pharmacodynamic evaluation (maximal electroshock method) was carried out for optimized complexes. Results: Molecular modeling approach and instrumental analysis (DSC, XRD, and FT-IR) confirmed the entrapment of CBZ inside the complexing agent. Increased solubility (∼1742%), sustained release (∼78%), better permeability (∼3.5 times), and enhanced pharmacodynamic responses conferred the best to 1:2 freeze dried (FD) and then 1:2 kneading (KD) complexes compared with pure CBZ. Conclusion: Now it could be concluded that HA may be tried as a complexing agent for antiepileptic drug and other classes of low water-soluble drug.

Glucosamine HCl as a new carrier for improved dissolution behaviour: Effect of grinding

The co-grinding technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs and it is superior to other approaches from an economical as well as an environmental stand point, as the technique does not require any toxic organic solvents. The present work is an attempt to use d-glucosamine HCl (G-HCl) as a potential excipient to improve dissolution rate of carbamazepine (CBZ) from physical mixtures and co-grinding formulations. The effect of order of grinding on dissolution of CBZ was also investigated. Co-ground of drug and G-HCL were prepared using different ratios using ball mill. The samples were subjected to different grinding times. In order to investigate the effect of grinding process on dissolution behaviour of CBZ, the drug was ground separately in the absence of glucosamine. Then the mixture of ground CBZ and un-ground d-glucosamine HCl were prepared. Physical mixtures of CBZ and G-HCl were also prepared for comparison. The properties of prepared co-ground systems and physical mixtures were studied using a dissolution tester, FT-IR, SEM, XRPD, and DSC. These results showed that the presence of glucosamine can increase dissolution rate of CBZ compared to pure CBZ. The results showed the order of grinding had a big impact on the dissolution performance of CBZ formulations containing glucosamine. All dissolution profiles generally showed that the fastest dissolution rate was obtained when ground CBZ was mixed with un-ground glucosamine. This was closely followed by the co-grinding of CBZ with glucosamine where lower grinding times showed the fastest dissolution. XRPD showed that the grinding of CBZ can reduce the percentage crystallinity of drug crystals. DSC study of ground CBZ showed that the grinding induced polymorphism transformations in the CBZ crystals and the limit and type of these transformations were related to the grinding time.

To enhance dissolution rate of poorly water-soluble drugs: Glucosamine hydrochloride as a potential carrier in solid dispersion formulations

The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however this is reliant on a suitable carrier and solvent being selected. The work presented explores d-glucosamine HCl (G-HCl) as a potential hydrophilic carrier to improve dissolution rate of a poorly water-soluble drug, carbamazepine (CBZ), from physical mixtures and solid dispersion formulations. The effect of different solvents in the preparation of solid dispersion formulations was also investigated. Solid dispersions of the drug and G-HCl were prepared using different ratios by the conventional solvent evaporation method. Different solvents (ethanol, acetone and water) were used as second variable in the preparation of solid dispersions. Physical mixtures of CBZ and G-HCl were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, FT-IR, SEM and DSC. These results showed that the presence of glucosamine can increase dissolution rate of CBZ compared to pure CBZ. All solid dispersions of CBZ–G-HCl showed considerably a higher dissolution rate than the corresponding physical mixtures. The presence of water during preparation of the solid dispersions reduced the dissolution rate of CBZ due to formation of carbamazepine dihydrate during the preparation of solid dispersion, as proved by DSC and FT-IR studies. To facilitate comparison, the dissolution efficiency was calculated for solid dispersions prepared with different solvents and the dissolution efficiency can generally be ranked as follows: ethanol > acetone > ethanol–water > acetone–water when the ratios of drug to carrier were 4:1 and 2:1. It has thus been shown that the use of G-HCl in solid dispersion formulations can significantly enhance the dissolution rate of poorly water-soluble drugs such as carbamazepine. This amino sugar could be used as a new carrier in solid dispersion formulations and would have significant commercial potential.

Preparation and evaluation of polymeric carbamazepin spherical crystals by emulsion solvent diffusion technique

In this study, a significant effect of different polymers on improving the solubility, dissolution rate, and physicochemical properties of carbamazepine (CBZ) has been demonstareted by emulsion solvent diffusion technique, with ethanol– chloroform–water as the solvent system. The hydrophilic polymers like polyethylene glycol, chitosan, and hydrophobic polymer Eudragit RSPO were used in the recrystallization process. The pure drug CBZ and the prepared spherical crystals of CBZ with different polymers were characterized in terms of morphology (microscopical photograph), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), drug contents, solubility, dissolution rate, crushing strength, wettability, flowability, and packability. The FTIR spectra of the prepared spherical crystals showed that changes in the chemical nature occur and do not present great fingerprint difference. The XRD also revealed a characteristic decrease in crystallinity. The solubility and dissolution studies demonstrated a marked increase in solubility and dissolution rate in comparison with the pure drug. The prepared spherical crystals with different polymers exhibited excellent physicochemical properties like flowability, packability, and wettability compared with the pure drug. The spherical crystals with polyethylene glycol and chitosan showed higher crushing strength when compared with the hydrophobic polymer (Eudragit RSPO).