Diffusion of a freely water-soluble drug in aqueous enteric-coated pellets

The effects of filler used in the pellet cores (ie, waxy cornstarch or lactose) and the enteric film coat thickness on the diffusion and dissolution of a freely soluble drug were studied. Two kinds of pellet cores containing riboflavin sodium phosphate as a model drug, microcrystalline cellulose (MCC) as a basic filler, and waxy cornstarch or lactose as a cofiller were film coated (theoretically weight increase 20% or 30%) with an aqueous dispersion of cellulose acetate phthalate (CAP). The diffusion of riboflavin sodium phosphate in aqueous enteric-coated pellets was investigated using noninvasive confocal laser scanning microscopy (CLSM). The in vitro release tests were performed using a USP apparatus I (basket method). Diffusion of drug from the core to the film coat was found to be greater with lactose-containing pellets than with waxy cornstarch-containing pellets. The dissolution test showed that 30% enteric-coated waxy cornstarch pellets had a good acidic resistance in 0.1 N HCl solution for at least 1 hour, while the other enteric pellet formulations failed the test. The waxy cornstarch-containing enteric pellets dissolved at SIF in less than 10 minutes. Confocal images of film-coated pellets showed that waxy cornstarch-containing pellets had less drug dissolved than respective lactose-containing pellets. The observations were further confirmed by measurement of fluorescence intensity of riboflavin sodium phosphate in the film coat. The dissolution test was consistent with the confocal microscopy results. In conclusion, waxy cornstarch as a cofiller in the pellet cores minimizes premature drug diffusion from the core into the film coat layer.     

The Use of ß-Cyclodextrin in the Manufacturing of Disintegrating Pellets with Improved Dissolution Performances

It has recently been highlighted that the release behavior of pellets containing microcystalline cellulose (MCC) as the spheronizing agent may be impaired by the lack of disintegration. Although alternative spheronizing excipients have been proposed, their overall advantages have not thoroughly been assessed. In the present work, the possible use of β-cyclodextrin (βCD) was therefore explored for the manufacturing of pellets with a potential for effective disintegration and immediate release of poorly soluble active ingredients. MCC/βCD powder formulations containing no drug or model drugs with different water solubility, able to form inclusion compounds with the employed cyclodextrin, were pelletized by agglomeration in rotary fluid bed equipment. By applying successive statistical experimental designs, the most critical formulation and operating parameters were identified and optimal manufacturing processes were ultimately set up. High yields of pellets provided with satisfactory physical-technological characteristics were obtained using powder formulations with up to 80% βCD. Based on dissolution testing results, the suitability of βCD for the preparation of disintegrating MCC-containing pellets with improved dissolution performance was finally demonstrated.     

In vitro drug permeation from chitosan pellets

The purpose of this study was to prepare and characterize coated pellets for controlled drug delivery. The influence of chitosan (CS) in pellets was evaluated by swelling, in vitro drug release and intestinal permeation assays. Pellets were coated with an enteric polymer, Kollicoat^® MAE 30 DP, in a fluidized-bed apparatus and the coating formulations were based on a factorial design. Metronidazole (MT) released from coated and uncoated pellets were assessed by dissolution method using Apparatus I. Intestinal permeation was evaluated by everted intestinal sac model in rats, used to study the absorption of MT from coated pellets containing CS or not through the intestinal tissue. Although the film coating avoided drug dissolution in gastric medium, the overall drug release and intestinal permeation were dependent on the presence of CS. Thus, pellets containing CS show potential as a system for controlled drug delivery.     

Solid-State Interactions at the Core-Coat Interface: Physicochemical Characterization of Enteric-Coated Omeprazole Pellets Without a Protective Sub-Coat

Conventionally, scanning electron or transmission microscopy, Raman and near infrared (NIR) spectroscopy, terahertz, florescence, and nuclear magnetic resonance imaging have been used to characterize functional coating structure. This study highlights the use of fluorescence microscopy to investigate the physicochemical stability and coating integrity of the commercially available enteric-coated omeprazole pellets containing a basic excipient and prepared by extrusion and spheronization or drug layering on the nonpareil seed, immediately followed by enteric coating (i.e., absence of protective sub-coat). The nature of coating interface and the likely development of an in situ interfacial layer after the application of enteric coating solution was examined using HPLC, NMR, differential scanning calorimetry (DSC), and fluorescent imaging methods. Likewise for the characterization of the solid pellet structure via fluorescence microscopy, a new approach based on fracturing technique (to avoid surface contamination) rather than microtome sectioning was used and validated. Analytical data showed that the pellets containing omeprazole remained chemically stable (>99.5% recovered). Control of the microenvironmental pH by the addition of alkalinizing excipient within a core formulation or as part of drug layering on top of nonpareil seed appears to efficiently neutralize the acidic effect of enteric coating dispersion. Fluorescence images further illustrate the absence of any discernable in situ layer formation at the coat-core interface.KEY WORDS: alkalinizing excipient, DSC, enteric coating, florescence microscopy, functional coating layer(s), HPLC, NMR, omeprazole stability     

Effect of Plasticizer on Release Kinetics of Diclofenac Sodium Pellets Coated with Eudragit RS 30 D

The present study was designed to investigate the effect of two plasticizers, i.e., triethyl citrate (TEC) and polyethylene glycol 6000 (PEG 6000) on the in vitro release kinetics of diclofenac sodium from sustained-release pellets. Ammonio methacrylate copolymer type B (Eudragit RS 30 D) is used as the release-retarding polymer. Both plasticizers were used at 10% and 15% (w/w) of Eudragit RS 30 D. Pellets were prepared by powder layering technology and coated with Eudragit RS 30 D by air suspension technique. Thermal properties of drug and drug-loaded beads were studied using differential scanning calorimeter (DSC). DSC thermogram represented the identity of raw materials and exhibited no interaction or complexation between the active and excipients used in the pelletization process. Dissolution study was performed by using USP apparatus 1. No significant difference was observed among the physical properties of the coated pellets of different batches. When dissolution was performed as pure drug, about 8.22% and 90% drug was dissolved at 2 h in 0.1 N HCl and at 30 min in buffer (pH 6.8), respectively. From all formulations, the release of drug in acid media was very negligible (maximum 1.8 ± 0.08% at 2 h) but in buffer only 12% and 30% drug was released at 10 h from coated pellets containing TEC and PEG 6000, respectively, indicating that Eudragit RS 30 D significantly retards the drug release rate and that drug release was varied according to the type and amount of plasticizers used. The amount of TEC in coating formulation significantly effected drug release (p < 0.001), but the effect of PEG 6000 was not significant. Formulations containing PEG 6000 released more drug (98.35 ± 2.35%) than TEC (68.01 ± 1.04%) after 24 h. Different kinetic models like zero order, first order, and Higuchi were used for fitting drug release pattern. Zero order model fitted best for diclofenac release in all formulations. Drug release mechanism was derived with Korsmeyer equation.     

Development and Characterization of Enteric-Coated Immediate-Release Pellets of Aceclofenac by Extrusion/Spheronization Technique Using κ-Carrageenan as a Pelletizing Agent

In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion–spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like β-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% κ-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of κ-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.     

Influence of operational variables on properties of piroxicam pellets prepared by extrusion-spheronization: A technical note

Summary and Conclusion  The processing conditions has a pronounced effect on the pellet properties. Drying conditions influenced the mean size and the drug release of the pellets. Because of the shrinking of the pellets upon drying at higher temperatures, the pellets also showed increased densities. Freeze drying almost prevented shrinking and thus led to the highest drug release. With an increase in the temperature of drying, the drug release rate decreased. Both spheronization time and spheronization speed affected the shapes of pellets, and the changes in shapes then affected the pellet flow properties. Within the studied range, the circularity of the pellets was affected more by the spheronization time than by the spheronization speed. Drying conditions influenced pellet friability, which decreased with an increase in drying temperature, indicating the formation of more dense structures at higher temperatures. The same result was obtained with spheronization time. With an increase in spheronization time, the friability decreased, because of the formation of more compact masses at higher spheronization time. Mean size was not affected by spheronization time or spheronization speed. Published: March 9, 2007     

Evaluation of Drug Release From Coated Pellets Based on Isomalt,Sugar, and Microcrystalline Cellulose Inert Cores

The objective of the present study was to investigate the effect of the pellet core materials isomalt, sugar, and microcrystalline cellulose on the in vitro drug release kinetics of coated sustained-release pellets as well as to evaluate the influence of different ratios of polymethacrylate copolymers exhibiting different permeability characteristics on the drug release rate. For characterization of the drug release process of pellets, the effect of osmolality was studied using glucose as an osmotically active agent in the dissolution medium. The pellet cores were layered with diclofenac sodium as model drug and coated with different ratios of Eudragit® RS30D and Eudragit® RL30D (ERS and ERL; 0:1 and 0.5:0.5 and 1:0 ratio) in a fluid bed apparatus. Physical characteristics such as mechanical strength, shape, and size proved that the inert cores were adequate for further processing. The in vitro dissolution tests were performed using a USP Apparatus I (basket method). The results demonstrated that, besides the ratio of the coating polymers (ERS/ERL), the release mechanism was also influenced by the type of starter core used. Sugar- and isomalt-type pellet cores demonstrated similar drug release profiles.     

Study of novel rosin-based biomaterials for pharmaceutical coating

The film forming and coating properties of Glycerol ester of maleic rosin (GMR) and Pentaerythritol ester of maleic rosin (PMR) were investigated. The 2 rosin-based biomaterials were initially characterized in terms of their physicochemical properties, molecular weight (Mw), and glass transition temperature (Tg). Films were produced by solvent evaporation technique on a mercury substrate. Dibutyl sebacate plasticized and nonplasticized films were characterized by mechanical (tensile zzzz strength, percentage elongation, and Young's modulus), water vapor transmission (WVT), and moisture absorption parameters. Plasticization was found to increase film elongation and decrease the Young's modulus, making the films more flexible and thereby reducing the brittleness. Poor rates of WVT and percentage moisture absorption were demonstrated by various film formulations. Diclofenac sodium-layered pellets coated with GMR and PMR film formulations showed sustained drug release for up to 10 hours. The release rate was influenced by the extent of plasticization and coating level. The results obtained in the study demonstrate the utility of novel rosin-based biomaterials for pharmaceutical coating and sustained-release drug delivery systems.     

Development of an Abuse- and Alcohol-Resistant Formulation Based on Hot-Melt Extrusion and Film Coating

This study focused on the development of flexible (i.e., deformable) multiple-unit pellets that feature (i) a prolonged drug release, (ii) drug abuse deterrence, and (iii) a minimal risk of alcohol-induced dose dumping (ADD). Deformable pellets were prepared via an advanced continuous one-step hot-melt extrusion (HME) technique, with the drug (i.e., antipyrine and codeine phosphate) fed as an aqueous solution into the molten matrix material (i.e., cornstarch, gum arabic, and xanthan). Formulations that had suitable mechanical characteristics (i.e., high compression strength) were coated with a flexible Aquacoat^® ARC film to ensure prolonged release and to avoid ADD. The pellets were characterized in terms of their mechanical properties and in vitro drug release behavior in alcoholic media. All formulations were abuse deterrent: they had a high compression strength and grinding the pellets into powder was impossible. Since the pellets comprising gum arabic and xanthan as a matrix did not remain intact during dissolution testing, they had a very fast drug release rate. Cornstarch-based pellets that swelled but remained intact in the dissolution media had a slower drug release. Coated cornstarch-based pellets had a prolonged release over 8 h and resistance to dose dumping in 20 and 40% ethanol. Our results indicate that cornstarch-based pellets manufactured via the advanced HME process followed by coating are a promising formulation that makes tampering difficult due to a high compression strength combined with robustness in alcoholic media.     

Preparation,Characterization and <Emphasis Type="Italic">In Vitro</Emphasis> / <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation of Oral Time-Controlled Release Etodolac Pellets

The objective of this study was to prepare time-controlled release etodolac pellets to facilitate drug administration according to the body’s biological rhythm, optimize the drug’s desired effects, and minimize adverse effects. The preparation consisted of three laminal layers from center to outside: the core, the swelling layer, and the insoluble polymer membrane. Factors influenced the core and the coating films were investigated in this study. The core pellets formulated with etodolac, lactose, and sodium carboxymethyl starch (CMS-Na) were prepared by extrusion-spheronization and then coated by a fluidized bed coater. Croscarmellose sodium (CC-Na) was selected as the swelling agent, and ethyl cellulose (EC) as the controlled release layer. The prepared pellets were characterized by scanning electron microscopy and evaluated by a dissolution test and a pharmacokinetic study. Compared with commercial available capsules, pharmacokinetics studies in beagle dogs indicated that the prepared pellets release the drug within a short period of time, immediately after a predetermined lag time. A good correlation between in vitro dissolution and in vivo absorption of the pellets was exhibited in the analysis.     

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     

Design and Evaluation of Self-Nanoemulsifying Pellets of Repaglinide

The aim of study was to develop self-nanoemulsifying pellets (SNEP) for oral delivery of poorly water soluble drug, repaglinide (RPG). Solubility of RPG in oily phases and surfactants was determined to identify components of self-nanoemulsifying drug delivery system (SNEDDS). The surfactants and cosurfactants were screened for their ability to emulsify oily phase. Ternary phase diagrams were constructed to identify nanoemulsification area for the selected systems. SNEDDS formulations with globule size less than 100 nm were evaluated for in vivo anti-hyperglycemic activity in neonatal streptozotocin rat model. A significant reduction in glucose levels was produced by optimized SNEDDS formulation in comparison to the control group. The optimized SNEDDS formulations were pelletized via extrusion/spheronization technique using microcrystalline cellulose and lactose. SNEP were characterized by X-ray powder diffraction and scanning electron microscopy. X-ray diffraction study indicated loss of crystallinity of RPG in SNEP. The SNEP exhibited good flow properties, mechanical strength and formed nanoemulsion with globule size less than 200 nm. SNEP showed in vitro release of more than 80% RPG in 10 min which was significantly higher than RPG containing reference pellets. In conclusion, our studies illustrated that RPG, a poorly water soluble drug can be successfully formulated into SNEP which can serve as a promising system for the delivery of poorly water soluble drugs.     

Influences of Sodium Carbonate on Physicochemical Properties of Lansoprazole in Designed Multiple Coating Pellets

Lansoprazole (LSP), a proton-pump inhibitor, belongs to class II drug. It is especially instable to heat, light, and acidic media, indicating that fabrication of a formulation stabilizing the drug is difficult. The addition of alkaline stabilizer is the most powerful method to protect the drug in solid formulations under detrimental environment. The purpose of the study was to characterize the designed multiple coating pellets of LSP containing an alkaline stabilizer (sodium carbonate) and assess the effect of the stabilizer on the physicochemical properties of the drug. The coated pellets were prepared by layer–layer film coating with a fluid-bed coater. In vitro release and acid-resistance studies were carried out in simulated gastric fluid and simulated intestinal fluid, respectively. Furthermore, the moisture-uptake test was performed to evaluate the influence of sodium carbonate on the drug stability. The results indicate that the drug exists in the amorphous state or small (nanometer size) particles without crystallization even after storage at 40°C/75% for 5 months. The addition of sodium carbonate to the pellet protects the drug from degradation in simulated gastric fluid in a dose-dependent manner. The moisture absorbed into the pellets has a detrimental effect on the drug stability. The extent of drug degradation is directly correlated with the content of moisture absorption. In conclusion, these results suggest that the presence of sodium carbonate influence the physicochemical properties of LSP, and the designed multiple coating pellets enhance the drug stability.     

Controlled Release of Oral Tetrahydrocurcumin from a Novel Self-Emulsifying Floating Drug Delivery System (SEFDDS)

The objectives of this study were to develop and evaluate a novel self-emulsifying floating drug delivery system (SEFDDS) that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis. The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate, pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose and transformed into pellets by the extrusion/spheronization technique. The resulting pellets with 22% liquid SEDDS had a uniform size and good self-emulsification property. The microemulsions in aqueous media of different self-emulsifying floating pellet formulations were in a particle size range of 25.9–32.5 nm. Use of different weight proportions of glyceryl behenate and sodium starch glycolate in pellet formulations had different effects on the floating abilities and in vitro drug release. The optimum formulation (F2) had a floating efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h period. The release rate and extent of release of THC liquid SEDDS (80% within 2 h) and self-emulsifying floating pellet formulation (80% within 8 h) were significantly higher than that of unformulated THC (only 30% within 8 h). The pellet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. Controlled release from this novel SEFDDS can be a useful alternative for the strategic development of oral solid lipid-based formulations.     

Development of polysaccharide gel-coated pellets for oral administration: swelling and release behavior of calcium pectinate gel

The aim of this study was to examine the effect of pellet size, pectin type, pectin concentration, and dissolution medium on the swelling and drug release behavior of spherical pellets containing theophylline and coated with 2 different calcium pectinates, using a multi-level factorial design approach. The spherical pellets were prepared by an extrusion-spheronization method and then coated with calcium pectinate using the diffusion-controlled interfacial complexation technique, which provides a defect-free and uniform coating on solid cores. Theophylline release from the pellets was slowed by the application of the coatings. The time to release 50% of the payload (ie, T50) in an acidic medium was approximately 7 minutes from uncoated small pellets and was 55 minutes after an amidated calcium pectinate coat was applied; a comparable coat on large pellets showed a T50 of 93 minutes. Drug release profiles of dry coated pellets showed a lag time (all less than 20 minutes) when the gel coat hydrated and swelled, followed by a zero-order release. It was found that the release rate was controlled by the pellet size, pectin type, pectin concentration, and dissolution medium.     

Development of formulations based on Streptomyces rochei strain PTL2 spores for biocontrol of Rhizoctonia solani damping-off of tomato seedlings

Rhizoctonia solani is one of the most problematic soil-borne pathogenic fungi for several crop cultures worldwide. This study highlights the effectiveness of high-antagonistic Streptomyces rochei strain PTL2, isolated from root tissues of Panicum turgidum, in controlling the R. solani damping-off and growth promotion of tomato (cv. Marmande) seedlings. The isolate PTL2 was characterised for in vitro biocontrol and plant growth-promoting traits. It exhibited remarkable positive results in all trials, including production of hydrogen cyanide, siderophores, 1-aminocyclopropane-1-carboxylate deaminase and phytohormones, chitinolytic activity and inorganic phosphate solubilisation. PTL2 spores were formulated as wettable talcum powder, sodium alginate pellets and sodium alginate-clay pellets. Their abilities in the biocontrol of R. solani and plant growth promotion were investigated in autoclaved and non-autoclaved soils. Talcum powder and sodium alginate pellets significantly reduced the damping-off severity index compared to a positive control. The talcum powder exhibited the highest protective activity, reducing the disease incidence from 89.3% to 14.1%, whereas chemical seed treatment with Thiram^® provided a disease incidence of 16.7%. Furthermore, the talc-based powder formulation resulted in greatest increases in the root length, shoot length and dry weight of seedlings. The interesting biocontrol potential and growth enhancement of tomato seedlings open up promising perspectives for the possible application of talcum powder formulation based on PTL2 spores in crop improvement.     

Effects of stabilizers on shelf-life of Epicoccum nigrum formulations and their relationship with biocontrol of postharvest brown rot by Monilinia of peaches

AIM: To find a formulation of Epicoccum nigrum conidia that maintains a high viability over time and which proves efficient to biocontrol peach rot caused by Monilinia spp. METHODS AND RESULTS: We tested the effect of stabilizers and desiccants on the shelf-life of Epicoccum nigrum conidia. Conidial samples were dried for 40 min at 40 degrees C in a fluidized bed-dryer to obtain moisture contents <15%. The toxicity of additives was tested by assaying production of conidia in fermentations and germinability of the produced conidia: 50% PEG300, 10%-5% KCl (stabilizers) and 95.24% Cl(2)Ca (desiccant) significantly (P = 0.05) reduced conidial germination. To enhance shelf-life of dried conidia, nontoxic stabilizers were added at the following different stages of the production-drying process: (i) to substrate contained in bags before production, (ii) to conidial centrifuge pellets obtained after production, before filtering and drying, (iii) to conidial centrifuge pellets obtained after production, before adding talc and drying, and (iv) to conidial centrifuge pellets obtained after production, before adding silica powder and drying. Conidial germinability was tested at 0, 180 and 365 days after storage at room temperature. Shelf-life of formulations retaining the highest viability were conidia produced with 1% KCl or 50% PEG 8000, conidia dried with 2.5% methylcellulose, and conidia dried with 1% KCl + silica powder. All these formulations improved the shelf-life of E. nigrum conidia and significantly reduced brown rot on peaches. CONCLUSIONS: Our results show that additives improve the shelf-life of E. nigrum and assist controlling brown rot on peaches. SIGNIFICANCE AND IMPACT OF THE STUDY: New improved formulations of a biocontrol agent have been obtained which will improve the control of Monilinia on peach.     

Exploring the Potential of A Highly Compressible Microcrystalline Cellulose as Novel Tabletting Excipient in the Compaction of Extended-Release Coated Pellets Containing an Extremely Water-Soluble Model Drug

Compaction of controlled-release coated pellets into tablets is challenging because of the fusion of pellets and the rupturing of coated film. The difficulty in compaction intensifies with the use of extremely water-soluble drugs. Therefore, the present study was conducted to prepare and compact pellets containing pseudoephedrine hydrochloride as an extremely water-soluble model drug. The pellets were produced using an extrusion–spheronization technique. The drug-loaded pellets were coated to extend the drug release up to 12-h employing various polymers, and then they were compressed into tablets using microcrystalline cellulose Ceolus KG-801 as a novel tabletting excipient. The in vitro drug release studies of coated pellets and tablets were undertaken using the USP basket method in dissolution test apparatus I. The amount of drug released was analyzed at a wavelength of 215 nm. The combined coatings of hydroxypropyl methylcellulose and Kollicoat SR-30D yielded 12-h extended-release pellets with drug release independent of pH of dissolution medium following zero-order kinetics. The drug release from the tablets prepared using inert Celous KG-801 granules as tabletting excipient was found faster than that of coated pellets. However, a modification in drug release rate occurred with the incorporation of inert Ceolus KG-801 pellets. The drug dissolution profile from tablets containing 40% w/w each of coated pellets and inert granules along with 20% w/w inert pellets was found to be closely similar to that of coated pellets. Furthermore, the friability, tensile strength, and disintegration time of the tablets were within the USP specifications.     

Physicomechanical Properties of Naproxen-Loaded Microparticles Prepared from Eudragit L100

Microparticles of naproxen with Eudragit L100 and Aerosil were prepared by the emulsion solvent diffusion method in order to avoid local gastrointestinal irritation, one of the major side effects of nonsteroidal anti-inflammatory drugs after oral ingestion. The process of preparation involved the use of ethanol as good solvent, dichloromethane as a bridging liquid, water as poor solvent, Aerosil as anti-adhesion agent, and sodium dodecyl sulfate to aid in the dispersion of the drug and excipients into the poor solvent. The obtained microparticles were evaluated for micromeritic properties, yield, encapsulation efficiency, drug physical state, and drug release properties. The influence of formulation factors and preparation condition (polymer/naproxen ratio, Aerosil/polymer ratio, and the initial difference of temperature between the solvent and nonsolvent) on the properties of the microparticles were also examined. The resultant microparticles were finely spherical and uniform with high incorporation efficiency (>79%) and yield (>71%). The incorporation efficiency was enhanced with increasing the ratio of excipients to drug and the initial difference of temperature between the solvent and nonsolvent. The mean diameter of the microparticles was influenced by all of the manufacturing parameters. Studies carried out to characterize the micromeritic properties of formulations, such as flowability and packability, showed that microparticles were suitable for further pharmaceutical manipulation (e.g., capsule filling). Drug release studies of the microparticles confirmed the gastroresistance, and mathematical studies showed that the drug released followed a Hixon and Crowell kinetic. These microparticles represent a simple method for the preparation of drug-loaded enteric microparticles with desired micromeritic properties and gastroresistance release.