Sustained Release Matrix Pellets Research Articles

Preparation and evaluation of lipid-based sustained release pellets of chlorpheniramine maleate by the wet extrusion-spheronization method

Introduction: This study aimed to investigate the feasibility of preparation of sustained-release chlorpheniramine maleate (CPM) pellets based on Compritol® as a lipid matrix and evaluation of the affecting factors on pellet properties. Methods: Using the D-optimal experimental design, different pellet formulations containing various amounts of CPM, Compritol® and Avicel were prepared by the wet extrusion-spheronization method. Then the pellets were cured at 40, 65 and 90 ̊C for 4 and 8 h to study the effect of the thermal process. The physicomechanical properties of the pellets were investigated in terms of particle size distribution, pelletization yield, mechanical strength, aspect ratio and sphericity. To investigate the possible interaction of CPM and Compritol®, as well as to evaluate the morphology and surface characteristics of the pellets DSC and SEM were used, respectively. Also, to investigate the drug release rate from pellets the dissolution test was carried out and mean dissolution time (MDT) was calculated to compare different formulations. Results: The results showed that the curing process up to 65 °C improves the strength of the pellets. However, increasing the curing temperature from 65 to 90 °C and also increasing the curing time from 4 to 8 h did not have a significant effect on the strength of the pellets but increased the drug release rate of pellets. Increasing the amount of the drug or decreasing Compritol® in the matrix of pellets leads to a larger particle size with greater mechanical strength. All formulations of the pellets had an aspect ratio and sphericity of about 1.1 and 0.9 respectively, which indicates the spherical shape of the pellets as shown by SEM. DSC thermograms indicate the reduction of the crystallinity or the change of the crystalline form of the drug to amorphous during the pelletization process. Conclusion: The results revealed the feasibility of preparing lipid-based sustained-release matrix pellets using the wet extrusion-spheronization method. The optimal formulation in terms of physicomechanical properties and release rate was the formulation containing 8% CPM, 67% Compritol® and 25% Avicel, which were dried at 40 ° C for 4 h and released about 90% of the drug within 12 h.

Preparation and evaluation of lipid-based sustained release pellets of chlorpheniramine maleate by the wet extrusion-spheronization method

Background: This study aimed to investigate the feasibility of preparation of sustained-release chlorpheniramine maleate (CPM) pellets based on Compritol® as a lipid matrix and evaluation of the affecting factors on pellet properties. Method: Using the D-optimal experimental design, different pellet formulations containing various amounts of CPM, Compritol® and Avicel were prepared by the wet extrusion-spheronization method. Then the pellets were cured at 40, 65 and 90 ̊C for 4 and 8 h to study the effect of the thermal process. The physicomechanical properties of the pellets were investigated in terms of particle size distribution, pelletization yield, mechanical strength, aspect ratio and sphericity. To investigate the possible interaction of CPM and Compritol®, as well as to evaluate the morphology and surface characteristics of the pellets DSC and SEM were used, respectively. Also, to investigate the drug release rate from pellets the dissolution test was carried out and mean dissolution time (MDT) was calculated to compare different formulations. Results: The results showed that the curing process up to 65 °C improves the strength of the pellets. However, increasing the curing temperature from 65 to 90 °C and also increasing the curing time from 4 to 8 h did not have a significant effect on the strength of the pellets but increased the drug release rate of pellets. Increasing the amount of the drug or decreasing Compritol® in the matrix of pellets leads to a larger particle size with greater mechanical strength. All formulations of the pellets had an aspect ratio and sphericity of about 1.1 and 0.9 respectively, which indicates the spherical shape of the pellets as shown by SEM. DSC thermograms indicate the reduction of the crystallinity or the change of the crystalline form of the drug to amorphous during the pelletization process. Conclusion: The results revealed the feasibility of preparing lipid-based sustained-release matrix pellets using the wet extrusion-spheronization method. The optimal formulation in terms of physicomechanical properties and release rate was the formulation containing 8% CPM, 67% Compritol® and 25% Avicel, which were dried at 40 ° C for 4h and released about 90% of the drug within 12 h.

Optimization and evaluation of Lisinopril mucoadhesive sustained release matrix pellets: In-vitro and ex-vivo studies

Lisinopril (LIS) is antihypertensive drug, classified as a class III drug with high water solubility and low permeability. To overcome the low permeability, 32 factorial designs aimed to formulate LIS as a sustained-release (LIS-SR) matrix pellet by extrusion/spheronization. Matrix pellets were composed of wet mass containing Avicel® and polymeric matrix polymers (sodium alginate (SA) and chitosan (CS)). Evaluation of the effect of two independent variables, matrix-forming units (SA and CS) on mean line torque, on pellet size, dissolution rate after 6 h, and mucoadhesion strength of the pellets were assessed using Statgraphics software. The tested formulations (F1-F9) showed that mean line torque ranged from 1.583 to 0.461 Nm, with LIS content in the LIS-SR pellets ranged from 87.9 to 103%, sizes varied from 1906 to 1404 µm and high percentages of drug released from pellets formulations (68.48 to 74.18 %), while the mean zeta potential value of mucoadhesive range from −17.5 to –22.9 mV.The selection of optimized formulation must have the following desirability: maximum peak torque, maximum pellets’ particle size, and minimum % LIS release after 6hr. LIS optimized sustained release pellet formula composed of 2,159 % SA and 0.357 % CS was chosen as optimized formula. It’s showed a 1.055 Nm mean line torque was responsible for the increased pellet size to 1830.8 μm with decreased release rate 56.2 % after 6 hr, and −20.33 mV average mucin zeta potential.Ex-vivo mucoadhesion studies revealed that that the optimize formulation, exhibited excellent mucoadhesive properties, after 1 h, about 73% of the pellets were still attached to the mucus membrane. Additionally, ex-vivo permeation determination of LIS from the optimized LIS-SR formulation was found to be significantly higher (1.7-folds) as compared to free LIS.In conclusion: LIS-SR matrix pellets, prepared with an extrusion/spheronization have desirable excellent characteristics in-vitro and ex-vivo sustained-release pellet formulation of LIS-SR was able to sustain the release of LIS for up to 8 h.

Impact of Selective Polymer on Optimization of Sustained Release Matrix Pellets of Sitagliptin

Pravina N Gurjar1 and Ashok V Bhosale2 Author informationArticle notesCopyright and License information 1PDEA’S Seth Govind Raghunath Sable College of Pharmacy, Saswad, Pune, Maharashtra, INDIA 2PDEA’s Shankarrao Ursal College of Pharmaceutical Sciences and Research Centre, Kharadi, Pune, Maharashtra, INDIA Corresponding author. Correspondence: Pravina N Gurjar Research Scholar, PDEA’S Seth Govind Raghunath Sable College of Pharmacy

Formulation Development of Sustained Release Matrix Pellets Compressed into Unit Dosage Form

>Any drug delivery system’s main objective is to consistently deliver the desired drug concentration in the blood or tissues, which is therapeutically beneficial and non-toxic. The spherical, free-flowing granules known as pellets increase bioavailability, lower the risk of dose dumping and local gastrointestinal discomfort, regulate drug release, and boost absorption of the medicine. A second-generation sulfonylurea called gliclazide is used to treat non-insulin-dependent diabetic mellitus (NIDDM). This study’s objectives were to construct a flexible dosage form with controlled release and look into how process parameters affected the procedure. To find the batch of pellets that provided a sustained release pattern for the drug gliclazide, several batches of pellets manufactured using the extrusion spheronization process and the design of experiment (DoE) approach were used. Due to their roundness, the pellets had excellent flow characteristics, which affected the dosage production rate. They also had small particles that could be easily dispersed and helped prevent dosing. The release rate of the pellets was 99.3% after 12 hours. With superior medication release control, the study completes the development of sustained-release pellets, minimizing issues with the conventional tablet administration form.

Development and Characterization of Eudragit-RL-100-Based Aceclofenac Sustained-Release Matrix Pellets Prepared via Extrusion/Spheronization.

Aceclofenac (AC) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain in conditions such as rheumatoid arthritis, with frequent administration during the day. The formulation of sustained release matrix pellets can provide a promising alternative dosage form that controls the release of the drug, with less blood fluctuation and side effects—especially those related to the gastric system. The extrusion/spheronization technique was used to formulate AC matrix pellets. The response surface methodology (version 17.2.02.; Statgraphics Centurion) was used to study the impacts of Eudragit RL 100 and PVP K90 binder solution concentrations on the pellets’ wet mass peak torque, pellet size, and the release of the drug. Statistically, a significant synergistic effect of PVP K90 concentration on the peak torque and pellet size was observed (p = 0.0156 and 0.031, respectively), while Eudragit RL 100 showed significant antagonistic effects (p = 0.042 and 0.013, respectively). The peak torque decreased from 0.513 ± 0.022 to 0.41 ± 0.021 when increasing the Eudragit RL 100 from 0 to 20%, and the pellet size decreased from 0.914 ± 0.047 to 0.789 ± 0.074 nm. The tested independent factors did not significantly affect the drug release in the acidic medium within 2 h, but these pellet formulae maintained the drug release at less than 10% in the acidic medium (pH 1.2), which may decrease gastric irritation side effects. In contrast, a highly significant synergistic effect of Eudragit and highly antagonistic effect of the PVP solution on drug release in the alkaline-pH medium were observed (p = 0.002 and 0.007, respectively). The optimized pellet formula derived from the statistical program, composed of 3.21% Eudragit and 5% PVP solution, showed peak torque of 0.861 ± 0.056 Nm and pellet size of 1090 ± 85 µm, and resulted in a significant retardation effect on the release after 8 h compared to the untreated drug.

Optimized flurbiprofen sustained-release matrix pellets prepared by extrusion/spheronization

Flurbiprofen (FBP) is an ibuprofen derivative with less gastric side effects and short biological half-life (4.7–5.7 h). The study aimed to formulate FBP as a sustained-release pellets by extrusion/spheronization to overcome its short half-life and to decrease dose frequency. The wet mass of the pellets containing Avicel® and a polymeric matrix polymer was determined by measuring the mean line torque. The impacts of different types and concentrations of matrix-forming units (HPMC, Carbopol, and PVP) (independent variables) on pellet size, mean line torque, and dissolution rate after 8 h were assessed using the Box-Behnken design. The results showed that the formulation containing higher concentrations of HPMC and Carbopol, such as F14, had high mean line torque value. This high mean line torque was responsible for the increased pellet size (>1100 μm) and decreased release rate (68 ± 2.8%) after 8 h of F14, compared with those of F5, which did not contain HPMC or Carbopol and had the lowest mean line torque, smallest pellet size (875.9 ± 27.5 μm), and highest dissolution rate after 8 h (100 ± 5.9%). In conclusion, sustained-release pellet formulation of FBP was able to sustain the release of FBP for up to 8 h.

Piperine fast disintegrating tablets comprising sustained-release matrix pellets with enhanced bioavailability: formulation, in vitro and in vivo evaluation

Piperine (Pip) has been widely studied for its multiple activities such as antidepressant, anti-epileptic, and so forth. However, the poor water solubility coupled with low bioavailability may inevitably hinder the application of Pip in the clinical setting. In this study, a formulation strategy was proposed to spontaneously resolve the low bioavailability and dose dividing issue of Pip. The matrix pellets (Pip-SR-pellets) consisting of Pip solid dispersion (Pip-SD) and hydroxypropylmethyl cellulose-K100 were developed to achieve an increased and sustained release profile in vitro. The Pip-SR-pellets were compacted into fast disintegrating tablets (FDTs) with a blend of excipients comprising lactose, MCC, LS-HPC, and CMS-Na. The Pip-SD was characterized by solubility study and XRD. The evaluation of the cross-sectional morphology of the Pip-FDTs via scanning electron microscope proved that Pip-SR-pellets maintained its structural integrity during compression and were uniformly distributed in the Pip-FDTs. The release profile of Pip-SR-pellets was highly consistent with the Pip-FDTs. In vivo pharmacokinetics study demonstrated that the relative bioavailability of Pip-SR-pellets was approximately 2.70-fold higher than that of the pure drug, and 1.62-fold compared with that of Pip-SD. This work therefore showed a potential industrialized method could be applied to formulate poorly water-soluble drug that has dose-dividing requirement.

Use of Black Gram Polysaccharide Mucilage as Release Retardant in the Development of Sustained Release Matrix Pellets of Ciprofloxacin Hydrochloride

Use of Black Gram Polysaccharide Mucilage as Release Retardant in the Development of Sustained Release Matrix Pellets of Ciprofloxacin Hydrochloride

Effect of wet mass on dextromethorphan hydrobromide matrix pellets

Dextromethorphan hydrobromide (DM) sustained release matrix pellets containing 10% w/w drug were prepared by an extrusion/spheronization technique. The effect of mixing different concentrations of ethyl cellulose (EC), hydroxypropyl methylcellulpse (HPMC K10), and Carbopol 934 with Avicel PH101 on the rheological properties of pellet wet mass was evaluated using mixer torque rheometry (MTR). The prepared pellets were characterized for size, drug content, and in-vitro DM release rate. The results showed that increasing the concentration of the hydrophobic polymer (EC) with Avicel PH101 decreased wet mass consistency, represented by mass mean line torque. Lower binder ratio was required for optimum wet massing, while mixing with swellable polymers (HPMC and Carbopol) caused a noticeable increase in both mean line torque and binder ratio. Combinations of HPMC and Carbopol at higher concentrations resulted in controlled in vitro release of DM from the prepared pellets. Furthermore, mathematical treatment of the in vitro release data of DM from the prepared pellets showed that all formulations except those containing 5% Carbopol plus 5% HPMC (F10) follow first order release. n values of these formulation were in the range of 0.09-0.40, which support an anomalous non-Fickian release.

Preparation and In Vitro-In Vivo Evaluation of Sustained-Release Matrix Pellets of Capsaicin to Enhance the Oral Bioavailability.

Capsaicin has multiple pharmacological activities including antioxidant, anticancer, and anti-inflammatory activities. However, its clinical application is limited due to its poor aqueous solubility, gastric irritation, and low oral bioavailability. This research was aimed at preparing sustained-release matrix pellets of capsaicin to enhance its oral bioavailability. The pellets comprised of a core of solid-dispersed capsaicin mixed with microcrystalline cellulose (MCC) and hydroxypropyl cellulose (HPMC) and subsequently coating with ethyl cellulose (EC) were obtained by using the technology of extrusion/spheronization. The physicochemical properties of the pellets were evaluated through scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD). Besides, the in vitro release, in vivo absorption, and in vitro-in vivo correlation were also assessed. More importantly, the relative bioavailability of the sustained-release matrix pellets was studied in fasted rabbits after oral administration using free capsaicin and solid dispersion as references. The oral bioavailability of the matrix pellets and sustained-release matrix pellets of capsaicin was improved approximately 1.98-fold and 5.34-fold, respectively, compared with the free capsaicin. A good level A IVIVC (in vitro-in vivo correlation) was established between the in vitro dissolution and the in vivo absorption of sustained-release matrix pellets. All the results affirmed the remarkable improvement in the oral bioavailability of capsaicin owing to the successful preparation of its sustained-release matrix pellets.

Preparation and evaluation of a controlled drug release of repaglinide through matrix pellets: in vitro and in vivo studies

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1 h. Designing a controlled release dosage form of the drug is required to maintain its therapeutic blood level and to eliminate its adverse effects, particularly the hypoglycaemia. Repaglinide sustained release matrix pellets consisting of Avicel, lactose and different polymers were prepared using extrusion–spheronisation method. The effect of different formulation components on in vitro drug release were evaluated using USP apparatus (paddle) for 12 h in phosphate buffer. The optimised formulation was orally administrated to normal and STZ induced diabetic rats. Most pellet formulations had acceptable physical properties with regard to size distribution, flowability and friability. Repaglinide pellets comprising Avicel 50%, lactose 47% and SLS 1% were released 94% of its drug content after 12 h. The optimised formulation was able to decrease blood glucose level in normal rats and those with diabetes throughout 8–12 h.

Formulation and evaluation of mefenamic acid sustained release matrix pellets

The objective of the study was to prepare mefenamic acid (MA) sustained release matrix pellets and investigate the formulation parameters affecting pellet attributes and drug release in vitro. Amixer torque rheometer (MTR) was used to characterize the rheological properties of wet mass used in pellet formulation. Mefenamic acid pellets were prepared by extrusion/spheronization techniques using microcrystalline cellulose (MCC) in combination with lactose as pellet forming agents and water as the binding liquid. Also, the prepared pellets were characterized for their particle size and in vitro drug dissolution. The results revealed that the increase in lactose weight ratio to MCC resulted in a significant reduction of both maximum torque and binder ratios, while the addition of 2 % (m/m) polyvinyl pyrolidone (PVP) to MCC-lactose influenced only the mean torque rather than the wetting liquid (water). Particle size ranged from 945 to 1089 mm and had small span values (0.56-0.67). Furthermore, an inverse relation was observed between the rheological character of pellet wet masses (expressed by peak torque) and in vitro release rate. Increasing MAloading from 2.5 to 5 and 10 % was accompanied by a decrease in dissolution rates. In conclusion, properties of MA matrix pellets could be successfully monitored by controlling the wet mass characteristics by measuring torque.

Development of novel sustained release matrix pellets of betahistine dihydrochloride: effect of lipophilic surfactants and co-surfactants

Sustained release matrix pellets of the freely water soluble drug, betahistine dihydrochloride (BH), were prepared using freeze pelletization technique. Different waxes and lipids (cetyl alcohol, beeswax, glyceryl tripalmitate (GTP) and glyceryl tristearate) were evaluated for the preparation of matrix pellets. A D-optimal design was employed for the optimization and to explore the effect of drug loading (X1), concentration of lipophilic surfactant (X2), concentration of co-surfactant (X3) and wax type (X4) on the release extent of the drug from matrix pellets. The entrapment efficiency (Y1), pellet diameter (Y2), and the percentage drug released at given times were selected as dependent variables. Results revealed a significant impact of all independent variables on drug release from the formulated pellets. The lipophilic surfactant significantly increased both the entrapment efficiency and the in vitro drug release and significantly decreased the pellet size. The optimized BH-loaded pellets were composed of 19.95% drug loading, 9.95% Span® 80 (surfactant), 0.25% Capmul® (co-surfactant) using glyceryl tripalmitate as a matrix former. The release profiles of the drug from hard gelatin capsule containing optimized pellets equivalent to 32 mg BH was similar to that of target release model for once-daily administration based on similarity factor. It could be concluded that a promising once-daily capsule containing sustained release pellets of BH was successfully designed.

Controlled-Release Pelletized Dosage Forms Using the Extrusion-Spheronization Process

ABSTRACT − Pellets, which are multiple-unit dosage systems, have the several therapeutic advantages over single-unitdosage systems in oral drug delivery. This review focuses on the current status and explores extrusion-spheronization tech-nique with special attention to controlled-release application of pellets including coated pellets for delayed release for-mulations, coated pellets for colon delivery, coated pellets for sustained drug delivery, sustained-release matrix pellets,pellets compressed into tablets, bioadhesive pellets, floating pellets, and pelletization with solubilization techniques.Key words − Pellets, Multiparticulates, Modified- release, Pelletization, Solubilization Pelletization process is an agglomeration process that resultsin agglomerates of a narrow size distribution in the range of0.5-1.5 mm with a low intra-agglomerate porosity (about 10%)and the higher density compared to the granules. Pellets areproduced by pelletization process and these agglomerates havethe relatively spherical shape, low friability and free flowingproperties, which facilitate the handling of pellets in the man-ufacturing process. Pelletization process can prevent the seg-regation of co-agglomerated components, resulting in animprovement of the content uniformity. Pelletization processcan also avoid the dust formation resulting in an improvementof the process safety, as fine powders can cause dust explo-sions and respiratory health problems. Pellets are widely usedin multiparticulate systems and multiparticulate systems havethe several therapeutic advantages over single-unit dosage sys-tems in oral drug delivery. The low inter- and intra-subjectvariability can be achieved by multiparticulate systems becausemultiparticulates can pass through the pylorus immediately afteradministration. Moreover, less effect of food on drug absorp-tion and rather uniform gastric emptying time than single-unitdosage systems can be attainable in multiparticulate systems.Safety concerns due to dose dumping of drugs, which havenarrow therapeutic index, is minimized in multiparticulate sys-tems, and more foreseeable drug delivery in sustained releaseformulation is possible because the total drug dose is dividedover many units, not in a single-unit system. The small size ofmultiparticulates also enables them to be well dispersed alongthe gastrointestinal (GI) tract, enhancing drug absorption andreducing the irritant effect that single-unit systems may causeto the mucosal lining, especially if remained for an extendedtime at a specific site. The spherical pellets can be coated withrate-controlling polymers or compressed into tablets to achievedelayed-release, extended-release, and targeted-release profiles.Multiparticulate systems with different dose strengths can beobtained from the same batch of drug-loaded pellets withoutadditional formulation or process modification. Pellets withdifferent drugs or with different release profiles can be blendedand formulated in a single-unit dosage form such as capsule,which promotes the delivery of two or more chemically com-patible or incompatible drugs at the same or different sites inthe GI tract.Although several pelletization techniques such as high-shear,fluid-bed, spray-drying, and rotary-granulation techniques, aredeveloped and available in the pharmaceutical industry, theextrusion-spheronization technique has certain advantagessuch as preparation of spherical pellets with uniform size andhigh-drug loading (up to 90%) at a moderate cost using min-imum excipients. In various pelletization techniques, thisreview focuses on the current status and explores extrusion-spheronization technique with special attention to controlledrelease application of pellets. A thorough discussion of processvariables for extrusion-spheronization or characterization of

Preparation and in vitro evaluation of gliclazide sustained-release matrix pellets: formulation and storage stability

Objective: Gliclazide-loaded matrix pellets consisting of ethylcellulose, microcrystalline cellulose (MCC), and sodium carboxymethyl starch were prepared by extrusion-spheronization. Method: To control the initial fast release of the matrix pellets, three coating methods were used: hot-melt coating, polymer aqueous dispersion film coating, and MCC powder coating. An orthogonal experiment (L9(3)) was applied to optimize the key process variables of MCC-powder coating. The in vitro dissolution profiles of the coating pellets were compared with the commercial tablets Diamicron® by the similarity factor (f2). The storage stability was measured to choose the best coating method. Result: Initial fast release was overcome by using the three coating methods. Rotation speed of friction plate and time of coating (addition of binder/coating agents) were both found to have the more important influence to drug release. The f2 values between the three coated pellets and the commercial product were all greater than 50. The results of storage-stability tests suggest that the pellets prepared by MCC-powder-coating method are stable for at least 6 months under stress conditions (40°C/75%RH), whereas the others failed. Conclusion: The MCC-powder-coating method offered the advantage of a one-step procedure compared with film coating and hot-melt coating.

Preparation of sustained release matrix pellets by melt agglomeration in the fluidized bed: Influence of formulation variables and modelling of agglomerate growth

The one-step preparation of sustained release matrix pellets, using a melting procedure in a fluidized bed apparatus, was tested in a 2 3 full factorial design of experiments, using microcrystalline wax as lipophilic binder, theophylline as model drug and talc as additional matrix forming agent. The three influence parameters were (A) size of binder particles, (B) fraction of theophylline in solid particles and (C) fraction of microcrystalline wax in formulation. The response variables were agglomerate size and size distribution, dissolution time, agglomerate crush resistance, sphericity, yield and porosity. Nearly spherical pellets comprising a smooth, closed surface could be obtained with the used method, exhibiting the hollow core typical for the immersion and layering mechanism. The reproducibility was very good concerning all responses. The size of agglomerates is proportional to the size of the binder particles, which serve as cores for pellet formation in the molten state in the fluidized bed. Additionally, the agglomerate size is influenced by the volume of the solid particles in relation to the binder particles, with more solid particles leading to larger agglomerates and vice versa. Dissolution times vary in a very wide range, resulting from the interplay between amount of drug in relation to the meltable matrix substance microcrystalline wax and the non-meltable matrix substance talc. The change of binder particle size does not lead to a structural change of the matrix; both dissolution times and porosity are not significantly altered. Agglomerate crush resistance is low due to the hollow core of the pellets. However, it is significantly increased if the volume fraction of microcrystalline wax in the matrix is high, which means that the matrix is mechanically better stabilized. A theoretical model has been established to quantitatively explain agglomerate growth and very good accordance of the full particle size distributions between predicted and actual values could be shown. A low volumetric binder to solids ratio is compensated by a more porous layer. On the basis of this model, in-depth understanding on the mechanism and influence of product properties could be gained; and an a priori estimation of particle size distributions for new formulas can be performed, with densities, formula, and binder particle size distribution as input parameters.

Designing, Optimisation & Characterization of Sustained Release Matrix Pellets Prepared by Extrusion Spheronization Containing Mixture of Proteolytic Enzymes

A method for developing sustained release multiple unit dosage form consisting of pellets of a proteolytic enzyme blend using extrusion spheronization as a process is demonstrated in this paper. Effect of Cellulose and Methacrylate based polymers and plasticizers on stability of the enzyme blend are determined. The effect of type & concentration of the sustained release polymer, spheronization rpm and plasticizer on the yield & sphericity of pellets is studied. The results indicated that the SR pellets could be formulated for this enzyme blend using both HPMC K15 and EUDRAGIT RSPO. The best rpm for spheronization turned out to be 1200 rpm. Use of plasticizer improved yield and sphericity. Triethyl citrate was better over polyethylene glycol 400 and EUDRAGIT RSPO was better over HPMC K15 with respect to yield and sphericity of pellets. The pellets could be suitably enteric coated for protection of enzyme blend in lower pH of GIT. The in vitro release profile indicated release extension could be extended up to 12 hours in intestinal condition postulating to an acceptable bioavailablity in vivo.

Wax-based sustained release matrix pellets prepared by a novel freeze pelletization technique: I. Formulation and process variables affecting pellet characteristics

A novel freeze pelletization technique was evaluated for the preparation of wax-based matrix pellets. Pellets containing either theophylline or diltiazem HCl were prepared using various waxes. In this technique, molten waxes along with a dispersed active ingredient were introduced as droplets into an inert and immiscible column of liquid to form pellets. An 80% (w/w) aqueous glycerol solution was found to be the most suitable column liquid for preparing spherical wax pellets. The physical stability of the molten wax suspensions was substantially improved by the addition of a 5% (w/w) colloidal silica gel. Pellet size obtained was directly proportional to the cubic root of the outer radius of the needle tip used to form pellets. Pellet size increased as the ratio of interfacial tension ( γ LL) to the density difference (Δ ρ) between the molten matrix and the column liquid increased. Moreover, an increase in the drug load of theophylline increased the pellet size. However, an addition of a surfactant to the matrix slightly decreased the pellet size. Microscopic studies indicated that theophylline was homogenously dispersed throughout the matrix and existed in a crystalline state at higher drug loads. The percent drug recoveries ranged from 90.7 to 102.3% with acceptable drug loads up to 20% (w/w). Therefore, wax pellets containing drugs of varying aqueous solubility were successfully prepared using this technique.

Wax-based sustained release matrix pellets prepared by a novel freeze pelletization technique: II. In vitro drug release studies and release mechanisms

A novel freeze pelletization technique was evaluated for the preparation of wax-based sustained release matrix pellets. Pellets containing water-soluble drugs were successfully prepared using a variety of waxes. The drug release significantly depended on the wax type used and the aqueous drug solubility. The drug release decreased as the hydrophobicity of wax increased and the drug release increased as the aqueous drug solubility increased. In glyceryl monostearate (GMS) pellets, drug release rate decreased as the loading of theophylline increased. On the contrary, the release rate increased as the drug loading of diltiazem HCl increased in Precirol pellets. Theophylline at low drug loads existed in a dissolved state in GMS pellets and the release followed desorption kinetics. At higher loads, theophylline existed in a crystalline state and the release followed dissolution-controlled constant release for all the waxes studied. However, with the addition of increasing amounts of Brij 76, theophylline release rate increased and the release mechanism shifted to diffusion-controlled square root time kinetics. But the release of diltiazem HCl from Precirol pellets at all drug loads, followed diffusion-controlled square root time kinetics. Therefore, pellets capable of providing a variety of release profiles for different drugs can be prepared using this freeze pelletization technique by suitably modifying the pellet forming matrix compositions.