Crystallo-co-agglomeration: A novel technique to obtain ibuprofen-paracetamol agglomerates

The purpose of this research was to obtain directly compressible agglomerates of ibuprofen-paracetamol containing a desired ratio of drugs using a crystallo-co-agglomeration technique. Crystallo-co-agglomeration is an extension of the spherical crystallization technique, which enables simultaneous crystallization and agglomeration of 2 or more drugs or crystallization of a drug and its simultaneous agglomeration with another drug or excipient. Dichloromethane (DCM)-water system containing polyethylene glycol (PEG) 6000, polyvinyl pyrollidone, and ethylcellulose was used as the crystallization system. DCM acted as a good solvent for ibuprofen and bridging liquid for agglomeration. The process was performed at pH 5, considering the low solubility of ibuprofen and the stability of paracetamol. Loss of paracetamol was reduced by maintaining a low process temperature and by the addition of dextrose as a solubility suppressant. The agglomerates were characterized by differential scanning calorimetry, powder x-ray diffraction (PXRD), and scanning electron microscopy and were evaluated for tableting properties. The spherical agglomerates contained an ibuprofen-paracetamol ratio in the range of 1.23 to 1.36. Micromeritic, mechanical, and compressional properties of the agglomerates were affected by incorporated polymer. The PXRD data showed reduction in intensities owing to dilution and reduced crystallinity. Thermal data showed interaction between components at higher temperature. Ethylcellulose imparted mechanical strength to the agglomerates as well as compacts. The agglomerates containing PEG have better comparessibility but drug release in the initial stages was affected owing to asperity melting, yielding harder compacts. The agglomeration and properties of agglomerates were influenced by the nature of polymer.     

Design and evaluation of deformable talc agglomerates prepared by crystallo-Co-agglomeration technique for generating heterogenous matrix

The crystallo-co-agglomeration technique was used to design directly compressible and deformable agglomerates of talc containing the low-dose drug bromhexine hydrochloride (BXH). The process of agglomeration involved the use of dichloromethane as a good solvent and bridging liquid for BXH, water as a poor solvent, talc as diluent, and Tween 80 to aid dispersion of BXH and diluent into the poor solvent. Hydroxypropyl methylcellulose (50 cps) 4% wt/wt was used to impart the desired mechanical strength and polyethylene glycol 6000 5% wt/wt was used to impart the desired sphericity to the agglomerates. Clarity of the supernatant was considered an endpoint for completion of the agglomeration process. The drug-to-talc ratio in optimized batch 1 (BT1) and batch 2 (BT2) was kept at 1:15.66 and 1:24, respectively. The spherical agglomerates obtained were evaluated for topographic, micromeritic, mechanical, deformation, compressional, and drug release properties. The agglomeration yield and drug entrapment for both batches were above 94% wt/wt. Crushing strength and friability studies showed good handling qualities of agglomerates. Heckel plot studies showed low mean yield pressure and high tensile strength, indicating excellent compressibility and compactibility of agglomerates. Diametral and axial fracture of compacts showed deformation of agglomerates revealing formation of a heterogeneous compact. Drug release was sustained for 9 hours and 5 hours from BT1 and BT2, respectively, in 0.1N HCl. Hence, the crystallo-co-agglomeration technique can be successfully used for obtaining spherical, deformable, and directly compressible agglomerates, generating a heterogeneous matrix system and providing sustained drug release. Published: July 27, 2007     

Design and evaluation of deformable talc agglomerates prepared by crystallo-co-agglomeration technique for generating heterogeneous matrix

The crystallo-co-agglomeration technique was used to design directly compressible and deformable agglomerates of talc containing the low-dose drug bromhexine hydrochloride (BXH). The process of agglomeration involved the use of dichloromethane as a good solvent and bridging liquid for BXH, water as a poor solvent, talc as diluent, and Tween 80 to aid dispersion of BXH and diluent into the poor solvent. Hydroxypropyl methylcellulose (50 cps) 4% wt/wt was used to impart the desired mechanical strength and polyethylene glycol 6000 5% wt/wt was used to impart the desired sphericity to the agglomerates. Clarity of the supernatant was considered an endpoint for completion of the agglomeration process. The drug-to-talc ratio in optimized batch 1 (BT1) and batch 2 (BT2) was kept at 1:15.66 and 1:24, respectively. The spherical agglomerates obtained were evaluated for topographic, micromeritic, mechanical, deformation, compressional, and drug release properties. The agglomeration yield and drug entrapment for both batches were above 94% wt/wt. Crushing strength and friability studies showed good handling qualities of agglomerates. Heckel plot studies showed low mean yield pressure and high tensile strength, indicating excellent compressibility and compactibility of agglomerates. Diametral and axial fracture of compacts showed deformation of agglomerates revealing formation of a heterogeneous compact. Drug release was sustained for 9 hours and 5 hours from BT1 and BT2, respectively, in 0.1N HCl. Hence, the crystallo-co-agglomeration technique can be successfully used for obtaining spherical, deformable, and directly compressible agglomerates, generating a heterogeneous matrix system and providing sustained drug release.     

Preparation of Spherical Crystal Agglomerates of Naproxen Containing Disintegrant for Direct Tablet Making by Spherical Crystallization Technique

The purpose of this research was to obtain directly compressible agglomerates of naproxen containing disintegrant by spherical crystallization technique. Acetone–water containing hydroxypropyl celloluse (HPC) and disintegrant was used as the crystallization system. In this study croscarmellose sodium (Ac–Di–Sol) was employed as disintegrant. The agglomerates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), and scanning electron microscopy and were evaluated for flow, packing and tableting properties and drug release. The growth of particle size and the spherical form of the agglomerates resulted in formation of products with good flow and packing properties. The improved compaction properties of the agglomerated crystals were due to their fragmentation occurred during compression. DSC and XRPD studies showed that naproxen particles, crystallized in the presence of HPC and Ac–Di–Sol did not undergo structural modifications. The dissolution rate of naproxen from tablets made of naproxen–(Ac–Di–Sol) agglomerates was enhanced significantly because of including the disintegrant in to the particles. This was attributed to an increase in the surface area of the practically water insoluble drug is exposed to the dissolution medium. In conclusion the spherical crystallization technique developed in this study is suitable for obtaining agglomerates of drug with disintegrant.     

Influence of chitosan type on the properties of extruded pellets with low amount of microcrystalline cellulose

The purpose of this research was to study the influence of type of chitosan with different molecular weights, ie, 190 and 419 kDa, on properties of pellets prepared by extrusion/ spheronization. The formulations, consisting of acetaminophen as model drug, chitosan, microcrystalline cellulose (MCC), and dibasic calcium phosphate dihydrate with/without sodium alginate, were extruded using a twin-screw extruder and water as the granulating liquid. With 30% wt/wt MCC and no added sodium alginate, spherical pellets were produced containing low and high molecular weight chitosan at a maximum amount of 60% and 40% wt/wt, respectively. With sodium alginate (2.5% wt/wt), pellets with either type of chitosan (60% wt/wt), MCC (17.5% wt/wt), and acetaminophen (20% wt/wt) could be produced indicating an improved pelletforming ability. Type and amount of chitosan and added sodium alginate affected physical properties of pellets including size, roundness, crushing force, and drug release. Low molecular weight chitosan produced pellets with higher mean diameter, sphericity, and crushing force. Additionally, the pellets made of low molecular weight chitosan and added sodium alginate showed faster drug release in 0.1 N HCl but had slower drug release in pH 7.4 phosphate buffer. This indicated that drug release from pellets could be modified by the molecular weight of chitosan. In conclusion, the molecular weight of chitosan had a major influence on formation, physical properties, and drug release from the obtained pellets. Published: August 10, 2007     

Porous polystyrene beads as carriers for self-emulsifying system containing loratadine

The aim of this study was to formulate a self-emulsifying system (SES) containing a lipophilic drug, loratadine, and to explore the potential of preformed porous polystyrene beads (PPB) to act as carriers for such SES. Isotropic SES was formulated, which comprised Captex 200 (63% wt/wt), Cremophore EL (16% wt/wt), Capmul MCM (16% wt/wt), and loratadine (5% wt/wt). SES was evaluated for droplet size, drug content, and in vitro drug release. SES was loaded into preformed and characterized PPB using solvent evaporation method. SES-loaded PPB were evaluated using scanning electron microscopy (SEM) for density, specific surface area (S_BET), loading efficiency, drug content, and in vitro drug release. After SES loading, specific surface area reduced drastically, indicating filling of PPB micropores with SES. Loading efficiency was least for small size (SS) and comparable for medium size (MS) and large size (LS) PPB fractions. In vitro drug release was rapid in case of SS beads due to the presence of SES near to surface. LS fraction showed inadequate drug release owing to presence of deeper micropores that resisted outward diffusion of entrapped SES. Leaching of SES from micropores was the rate-limiting step for drug release. Geometrical features such as bead size and pore architecture of PPB were found to govern the loading efficiency and in vitro drug release from SES-loaded PPB. Published: March 24, 2006     

Preparation and characterization of flurbiprofen beads by melt solidification technique

Amelt solidification technique has been developed to obtain sustained-release waxy beads of flurbiprofen. Low glass transition temperature (t _g) and shear-induced crystallization of flurbiprofen made it a suitable candidate for melt solidification technique. The process involved emulsification and solidification of flurbiprofen-cetyl alcohol melt at significantly low temperature (5°C). The effect of variables, namely, the amount of cetyl alcohol and the speed of agitation, was studied using 3² factorial design. The technique and the beads were evaluated on the basis of process and desired yield, surface topography, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), particle size distribution, crushing strength, and drug release. Average values for process and desired yields were 97% wt/wt and 26% wt/wt, respectively. No interaction was observed between drug and excipient. Multiple regression analysis was carried out, and response surfaces were obtained. A curvilinear relationship was observed between percentage of desired yield and the amount of cetyl alcohol. Linear decrease in crushing strength was observed with increase in the amount of cetyl alcohol. Drug released from the beads followed zero order kinetics. Burst release was shown to a greater extent in beads containing a lower amount of cetyl alcohol. Response surfaces of time required for certain percentage of drug (t _D%) showed that after critical concentration of about 20% of cetyl alcohol (400 mg/batch), no significant release retardant effect was observed.     

Melt solidification technique: Incorporation of higher wax content in ibuprofen beads

The purpose of this study was to achieve incorporation of a higher amount of wax during the preparation of ibuprofen beads by a melt solidification technique for better integrity and prolonged drug release by using a combination of waxes. A mixture of cetyl alcohol (CA) and palmitic acid (PA) was used to improve the matrix integrity and drug release. The effect of variables such as CA, PA, and speed of agitation were studied using 3³ factorial design. Yield, crushing strength, and drug release were analyzed using response surface methodology. The in vitro dissolution test did not show any significant improvement in the drug release. Scanning electron microscopy (SEM) showed that beads were spherical with a smooth surface, but after dissolution became rough and porous. Differential scanning calorimetry (DSC) studies showed that different solidification and erosion properties of waxes are responsible for the inability of waxes to retard drug release even at higher concentration.     

The effect of drug concentration and curing time on processing and properties of calcium alginate beads containing metronidazole by response surface methodology

The purpose of present research work was to prepare calcium alginate beads containing water-soluble drug metronidazole using 3² factorial design, with drug concentration and curing time as variables. Curing time was kept as low as possible to improve entrapment with increasing drug concentration. Mostly the drugs which had been encapsulated were water insoluble to facilitate drug encapsulation; a characteristic drug release as whole process is aqueous based. Entrapment efficiency was in the range of 81% to 96% wt/wt, which decreased with decrease in polymer concentration and increase in curing time. The beads were spherical with size range between 1.4 and 1.9 mm. Scanning electron microscope (SEM) photomicrographs revealed increase in the leaching of drug crystals with increased curing time and high drug concentrations. In acidic environment, the swelling ratio was 200% in 30 minutes, but in basic medium, it increased to a maximum of 1400% within 120 minutes. In acidic medium, the swelling and drug release properties were influenced by drug solubility, whereas in phosphate buffer these properties were governed by the gelling of polymer and exhibited curvilinear and quadratic functions of both the variables, respectively.     

In vitro and in vivo evaluation of guar gum matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride

The objective of the study was to develop guar gum matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride. Matrix tablets of diltiazem hydrochloride, using various viscosity grades of guar gum in 2 proportions, were prepared by wet granulation method and subjected to in vitro drug release studies. Diltiazem hydrochloride matrix tablets containing either 30% wt/wt lowviscosity (LM1), 40% wt/wt medium-viscosity (MM2), or 50% wt/wt high-viscosity (HM2) guar gum showed controlled release. The drug release from all guar gum matrix tablets followed first-order kinetics via Fickian-diffusion. Further, the results of in vitro drug release studies in simulated gastrointestinal and colonic fluids showed that HM2 tablets provided controlled release comparable with marketed sustained release diltiazem hydrochloride tablets (D-SR tablets). Guar gum matrix tablets HM2 showed no change in physical appearance, drug content, or in dissolution pattern after storage at 40°C/relative humidity 75% for 6 months. When subjectd to in vivo pharmacokinetic evaluation in healthy volunteers, the HM2 tablets provided a slow and prolonged drug release when compared with D-SR tablets. Based on the results of in vitro and in vivo studies it was concluded that that guar gum matrix tablets provided oral controlled release of water-soluble diltiazem hydrochloride. Published: June 30, 2005     

Influence of ibuprofen as a solid-state plasticizer in eudragit® RS 30 D on the physicochemical properties of coated beads

The purpose of this study was to investigate the physicochemical properties of nonpareil beads coated with Eudragit RS 30 D containing ibuprofen as a multifunctional agent. The influence of the concentration of ibuprofen in the film coating and the effect of the coating level on drug release from coated beads was determined in pH 7.2 phosphate buffer solution. The influence of storage time at 23 degrees C and 60 degrees C on the release of ibuprofen from coated beads was also investigated. The thermal properties of the films were determined using a differential scanning calorimeter. Scanning electron microscopy was employed to image the surface morphology of the coated beads. Infrared spectroscopy was used to study the interaction of Eudragit RS 30 D and ibuprofen. Results from the dissolution studies demonstrated that increasing the amount of ibuprofen in the polymeric film reduced the rate of drug release, mainly because of a more complete coalescence of the polymeric particles of the latex dispersion. The glass transition temperature (Tg) of Eudragit RS 30 D films decreased and the surface of the coated beads became smoother as the concentration of ibuprofen was increased. Hydrogen bonding between the polymer and ibuprofen was demonstrated by Fourier transform infrared spectroscopy. No significant differences were found in drug dissolution between the coated beads stored at 23 degrees C for 12 months and those stored at 60 degrees C for 12 hours. The results of this study demonstrated that the ibuprofen plasticized the Eudragit RS 30 D. Furthermore, the dissolution rate of ibuprofen can be controlled and changes in the drug release rate can be minimized by using the drug-induced plasticization technique with this polymer.     

Effect of Eudragit<Superscript>®</Superscript> RS 30D and Talc Powder on Verapamil Hydrochloride Release from Beads Coated with Drug Layered Matrices

The aim of this study was to investigate the effect of Eudragit RS 30D, talc, and verapamil hydrochloride on dissolution and mechanical properties of beads coated with "drug-layered matrices". This was accomplished with the aid of a three-factor multiple-level factorial design using percent drug release in 1 and 2 h, T(50), tensile strength, brittleness, stiffness and toughness as the responses. Beads were coated in a fluidized-bed coating unit. Surface morphology and mechanical properties were evaluated by surface profilometry and texture analysis, respectively. No cracks, flaws and fissures were observed on the surfaces. The mechanical properties were dependent on the talc/polymer ratio. The release of verapamil from the beads was influenced by matrix components. Increasing the level of both talc and Eudragit decreased the percent drug released from 67% to 4.8% and from 80.7% to 6.7% in 1 and 2 h, respectively, and increased T(50) from 0.8 to 25.7 h. It was concluded that beads could be efficiently coated with "drug-layered matrices". The release of drug, however, depends on a balance between the levels of drug, talc, and polymer, whereby desired dissolution and mechanical properties could be controlled by the talc/polymer ratio and the level of drug loading.     

Modulation and Optimization of Drug Release from Uncoated Low Density Porous Carrier Based Delivery System

The purpose of this research work was to explore an application of uncoated porous drug carrier prepared by single-step drug adsorption for a delivery system based on integration of floating and pulsatile principles intended for chronotherapy. This objective was achieved by utilizing 3² factorial design, solvent volume (X ₁) and drug amount (X ₂) as selected variables, for drug adsorption using solvents, methanol, and dichloromethane (DCM), of varying polarity. Nitrogen adsorption (N₂), scanning electron microscopy of cross-sections, and atomic force microscopy were done to study adsorption patterns and their effect on release pattern. Drug release study was customized by performing for 6 h in acidic environment to mimic gastroretention followed by basic environment akin to transit phase. Correlation between porous data from mercury and N₂ adsorption was probably studied for the first time. Observed regression analysis values for pore volume, surface area, and drug release indicated the influence of selected variables. Total release range in acidic medium was 12.77–24.57% for methanol, 8.79–15.26% for DCM, and final release of 69.45–92.23% for methanol, and 60.16–99.99% for DCM influenced by varying internal geometries was observed. Present form of drug delivery system devoid of any additives/excipients influencing drug release shows distinct behavior from other approaches/technologies in chronotherapy by (a) observing desired low drug release (8%) in acidic medium, (b) overcoming the limitations of process variables caused by multiple formulation steps and different characteristic polymers, (c) reducing time consumption due to single step process, and (d) extending as controlled/extended release.     

Effect of Antiadherents on the Physical and Drug Release Properties of Acrylic Polymeric Films

Antiadherents are used to decrease tackiness of a polymer coating during both processing and subsequent storage. Despite being a common excipient in coating formulae, antiadherents may affect mechanical properties of the coating film as well as drug release from film-coated tablets, but how could addition of antiadherents affect these properties and to what extent and is there a relation between the physical characteristics of the tablet coat and the drug release mechanisms? The aim of this study was to evaluate physical characteristics of films containing different amounts of the antiadherents talc, glyceryl monostearate, and PlasACRYL^TM T20. Eudragit RL30D and Eudragit RS30D as sustained release polymers and Eudragit FS30D as a delayed release material were used. Polymer films were characterized by tensile testing, differential scanning calorimetry (DSC), microscopic examination, and water content as calculated from loss on drying. The effect of antiadherents on in vitro drug release for the model acetylsalicylic acid tablets coated with Eudragit FS30D was also determined. Increasing talc concentration was found to decrease the ability of the polymer films to resist mechanical stress. In contrast, glyceryl monostearate (GMS) and PlasACRYL produced more elastic films. Talc at concentrations higher than 25% caused negative effects, which make 25% concentration recommended to be used with acrylic polymers. All antiadherents delayed the drug release at all coating levels; hence, different tailoring of drug release may be achieved by adjusting antiadherent concentration with coating level.     

Nanoparticles containing ketoprofen and acrylic polymers prepared by an aerosol flow reactor method

The purpose of this study was to outline the effects of interactions between a model drug and various acrylic polymers on the physical properties of nanoparticles prepared by an aerosol flow reactor method. The amount of model drug, ketoprofen, in the nanoparticles was varied, and the nanoparticles were analyzed for particle size distribution, particle morphology, thermal properties, IR spectroscopy, and drug release. The nanoparticles produced were spherical, amorphous, and had a matrix-type structure. Ketoprofen crystallization was observed when the amount of drug in Eudragit L nanoparticles was more than 33% (wt/wt). For Eudragit E and Eudragit RS nanoparticles, the drug acted as an effective plasticizer resulting in lowering of the glass transition of the polymer. Two factors affected the preparation of nanoparticles by the aerosol flow reactor method, namely, the solubility of the drug in the polymer matrix and the thermal properties of the resulting drug-polymer matrix.     

Influence of Drug-to-Lipid Ratio on Drug Release Properties and Liposome Integrity in Liposomal Doxorubicin Formulations

Recent studies have shown that the release properties of vincristine encapsulated in large unilamellar vesicles (LUV) can be regulated by varying the drug-to-lipid (D/L) ratio. In this work it is shown that the drug-to-lipid ratio technique for regulating drug release also applies to doxorubicin encapsulated in LUV. In particular it is shown that the half-times (T_1/2) for doxorubicin release from distearoylphosphatidylcholine (DSPC)/cholesterol LUV in vitro can be increased more than six-fold by increasing the D/L ratio from 0.05 (wt/wt) to 0.39 (wt/wt). This behavior is consistent with the behavior expected for drugs that precipitate following accumulation into liposomes. It is shown that the release properties of ciprofloxacin—a drug that does not precipitate following accumulation into LUV—are not affected by the D/L ratio. It is also shown that the crystalline intravesicular doxorubicin precipitates observed as the D/L ratio is raised from 0.05 to 0.46 adopt increasingly unusual morphologies. Linear crystals are observed at lower D/L values, however triangular and rectangular variations are observed as the D/L ratio is increased, and induce considerable distortion in vesicle morphology. It is noted that trapping efficiency following uptake of external doxorubicin into LUV is reduced from nearly 100% at a D/L ratio of 0.05 (wt/wt) to less than 70% at an (initial) D/L ratio of 0.8 (wt/wt). It is suggested that this arises, at least in part, from membrane-disrupting effects of internal drug crystals as they increase in size.     

Preparation of biodegradable microspheres and matrix devices containing naltrexone

In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose, poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied. As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 μm to 104 μm. The drug release rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a PLA microparticulate system or matrix devices.     

Study of the Potential of Amphiphilic Conetworks Based on Poly(2-ethyl-2-oxazoline) as New Platforms for Delivery of Drugs with Limited Solubility

Thermoresponsive amphiphilic conetworks comprising poly(2-ethyl-2-oxazoline) (PEtOx), 2-hydroxyethyl methacrylate, and 2-hydroxypropyl acrylate segments have been studied as new platforms for delivery of drug with limited solubility. Series of conetworks of varied composition were synthesized and swelling kinetics in aqueous media and ethanol were followed. The platforms were loaded with the hydrophobic drug ibuprofen by swelling in its ethanol solution. The structure and properties of the drug carriers were investigated by scanning electron microscopy and differential scanning calorimetry. The release kinetics profiles of ibuprofen from the studied platform were established. The investigation proved the feasibility of the PEtOx-based amphiphilic conetworks as highly effective platforms for sustained ibuprofen delivery.     

A bioresorbable, polylactide reservoir for diffusional and osmotically controlled drug delivery

The purpose of this study was to design and characterize a zero-order bioresorbable reservoir delivery system (BRDS) for diffusional or osmotically controlled delivery of model drugs including macromolecules. The BRDS was manufactured by casting hollow cylindrical poly (lactic acid) (PLA): polyethylene glycol (PEG) membranes (10 x 1.6 mm) on a stainless steel mold. Physical properties of the PLA:PEG membranes were characterized by solid-state thermal analysis. After filling with drug (5 fluorouracil [5FU] or fluorescein isothiocyanate [FITC]-dextran:mannitol, 5:95 wt/wt mixture) and sealing with viscous PLA solution, cumulative in vitro dissolution studies were performed and drug release monitored by ultraviolet (UV) or florescence spectroscopy. Statistical analysis was performed using Minitab (Version 12). Differential scanning calorimetry thermograms of PLA:PEG membranes dried at 25 degrees C lacked the crystallization exotherms, dual endothermal melting peaks, and endothermal glass transition observed in PLA membranes dried at -25 degrees C. In vitro release studies demonstrated zero-order release of 5FU for up to 6 weeks from BRDS manufactured with 50% wt/wt PEG (drying temperature, 25 degrees C). The release of FITC dextrans of molecular weights 4400, 42 000, 148 000, and 464 000 followed zero-order kinetics that were independent of the dextran molecular weight. When monitored under different concentrations of urea in the dissolution medium, the release rate of FITC dextran 42 000 showed a linear correlation with the calculated osmotic gradient(DeltaPi). This study concludes that PEG inclusion at 25 degrees C enables manufacture of uniform, cylindrical PLA membranes of controlled permeability. The absence of molecular weight effects and a linear dependence of FITC-dextran release rate on DeltaPi confirm that the BRDS can be modified to release model macromolecules by an osmotically controlled mechanism.     

Cross-linked guar gum microspheres: A viable approach for improved delivery of anticancer drugs for the treatment of colorectal cancer

In the present work, guar gum microspheres containing methotrexate (MTX) were prepared and characterized for local release of drug in the colon, which is a prerequisite for the effective treatment of colorectal cancer. Guar gum microspheres were prepared by the emulsification method using glutaraldehyde as a cross-linking agent. Surface morphological characteristics were investigated using scanning electron microscopy. Particle size, shape, and surface morphology were significantly affected by guar gum concentration, glutaral dehyde concentration, emulsifier concentration (Span 80), stirring rate, stirring time, and operating temperature. MTX-loaded microspheres demonstrated high entrapment efficiency (75.7%). The in vitro drug release was investigated using a US Pharmacopeia paddle type (type II) dissolution rate test apparatus in different media (phosphate-buffered saline [PBS], gastrointestinal fluid of different pH, and rat cecal content release medium), which was found to be affected by a change to the guar gum concentration and glutaraldehyde concentration. The drug release in PBS (pH 7.4) and simulated gastric fluids followed a similar pattern and had a similar release rate, while a significant increase in percent cumulative drug release (91.0%) was observed in the medium containing rat cecal content. In in vivo studies, guar gum microspheres delivered most of their drug load (79.0%) to the colon, whereas plain drug suspensions could deliver only 23% of their total dose to the target site. Guar gum microspheres showed adequate potential in achieving local release of drug in in vitro release studies, and this finding was further endorsed with in vivo studies. Published: September 8, 2006