Matrix Pellets Research Articles

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury.

In addition to the loss of motor function, ~60% of patients develop pain after spinal cord injury. The cellular-molecular mechanisms are not well understood, but the data suggests that plasticity within the rostral, epicenter, and caudal penumbra of the injury site initiates a cellular-molecular interplay that acts as a rewiring mechanism leading to central neuropathic pain. Sprouting can lead to the formation of new connections triggering abnormal sensory transmission. The excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and excitotoxicity. Our previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator tamoxifen. In this study, we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord injury. We hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters, leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant sprouting. Male and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control (placebo). We used von Frey monofilaments and the "up-down method" to evaluate mechanical allodynia. Tamoxifen treatment decreased allodynia only in female rats with spinal cord injury revealing a sex-dependent effect. The expression profile of glutamatergic transporters (excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1) revealed a sexual dimorphism in the rostral, epicenter, and caudal areas of the spinal cord with a pattern of expression primarily on astrocytes. Female rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased excitatory amino acid transporter-2 expression compared with female rodents. Analyses of peptidergic (calcitonin gene-related peptide-α) and non-peptidergic (isolectin B4) fibers outgrowth in the dorsal horn after spinal cord injury showed an increased calcitonin gene-related peptide-α/ isolectin B4 ratio in comparison with sham, suggesting increased receptive fields in the dorsal horn. Although the behavioral assay shows decreased allodynia in tamoxifen-treated female rats, this was not associated with overexpression of glutamate transporters or alterations in the dorsal horn laminae fibers at 28 days post-injury. Our findings provide new evidence of the sexually dimorphic expression of glutamate transporters in the spinal cord. The dimorphic expression revealed in this study provides a therapeutic opportunity for treating chronic pain, an area with a critical need for treatment.

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.

Formulation and Evaluation of Taste Masked Chewable Tablet containing Curcumin, Acetaminophen, and Ascorbic acid to treat sore throat

Objective: This study was intended to investigate the formulation and characterization of Mesalamine or 5-Aminosalicylic acid (5-ASA) pellets using novel excipient and formulated as matrix spheres to controlled the drug release extended period of time. Uniformly distributed throughout the gastrointestinal tract and Avoid dose dumping of drug. Methods: Mesalamine's active pharmaceutical component was characterised, and investigations were conducted prior to formulation to ensure a physical combination of the drug and excipients was achieved. Formulation of mesalamine as matrix pellets by using fluid bed processor and mesalamine loaded into seal coated sugar spheres and extended-release coating with Ethyl cellulose. Ethyl cellulose is pH independent polymer and retarder the drug release throughout the gastrointestinal tract and site-specific action in colon. Hypromellose also act as pore former and drug release based on diffusion mechanism. In drug layering, core pellets contain stearic acid and hydrogenated castor oil internally forming a matrix. Developed mesalamine pellets are characterized such as drug content, invitro drug release and appearances and particle size distribution. Results: Development of Mesalamine pellets based on five strategy From MEZ 1 to MEZ 5 are formulated and Characterization are performed. Based on the invitro drug release studies, we concluded that the formulation MEZ-IV was best formulation. Invitro drug release is consistence throughout 12hours.(1hrs-23%, 2nd hrs 41%, 4hrs-73, 6hrs-86, 8hrs-99% and 12hrs-10.

Gas Chromatography with Modified pH‐sensitive Pellets in Evaluating the Activity of Some Enzymes Attributed with a Change in the Medium pH

A new evaluation method based on gas chromatography (GC) is considered for the screening of the inhibitory activity of various compounds against certain enzymes using immobilized pH-sensitive matrix pellets. This approach of analysis is being utilized in developing sensitive GC methods for enzymes attributed to pH change in their media. Particularly, for those which require accurate and sensitive assay methods. The method has been implemented in drug discovery research related to antagonism of carbonic anhydrase, isozyme 3 (CAIII). This isozyme has a strong potential in treating obesity, hyperlipidemia and cancer. The method was also used in investigation of various peptide derivatives with an epoxide warhead for their anti-lipase activity. Recently, the method has been used in evaluating some tacrine analogues for their inhibition against acetylcholinesterase enzyme. The latter is important in treating Alzheimer’s disease (AD) which is a worldwide mental disorder manifested with dementia symptoms and anticipated to be the second causality of deaths by 2040.

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.

Comparison of 5-ASA layered or matrix pellets coated with a combination of ethylcellulose and eudragits L and s in the treatment of ulcerative colitis in rats

The aim of this study was to evaluate and optimize the combination of time and pH-dependent polymers as a single coating for the design of the colon-specific drug delivery system of 5-aminosalicylic acid (5-ASA) pellets. 5-ASA matrix pellets with a 70% drug load were prepared by the extrusion-spheronization method. The optimal coating formula which included Eudragit S (ES) + Eudragit L (EL) + Ethylcellulose (EC) was predicted for the targeted drug delivery to the colonic area by a 32 factorial design. The ratio of ES:EL:EC and coating level were considered as independent variables while the responses were the release of less than 10% of the drug within 2 h (Y1), the release of 60–70% within 10 h at pH 6.8 (Y2) and lag time of less than 1 h at pH 7.2 (Y3). Also, 5-ASA layered pellets were prepared by the powder layering of 5-ASA on nonpareils (0.4–0.6 mm) in a fluidized bed coater and then coated with the same optimum coating composition. The coated 5-ASA layered or matrix pellets were tested in a rat model of ulcerative colitis (UC) and compared with the commercial form of 5-ASA pellets (Pentasa®). The ratio of ES:EL:EC of 33:52:15 w/w at a coating level of 7% was discovered as the optimum coating for the delivery of 5-ASA matrix pellets to the colon. The coated 5-ASA pellets were spherical with uniform coating as shown by SEM and met all of our release criteria as predicted. In-vivo studies demonstrated that the optimum 5-ASA layered or matrix pellets had superior anti-inflammatory activities than Pentasa® in terms of colitis activity index (CAI), colon damage score (CDS), colon/body weight ratio and colon’s tissue enzymes of glutathione (GSH) and malondialdehyde (MDA). The optimum coating formulation showed a high potential for colonic delivery of 5-ASA layered or matrix pellets and triggered drug release based on pH and time.

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, evaluation, and optimization of the omeprazole magnesium multi-unit particulate controlled release tablets using different concentrations of polymers

Multi-Unit Particulates (MUPs) with matrix pellets are used to develop controlled release products of various active pharmaceutical ingredients. They may allow improvement in solubility and thereby bioavailability of poorly soluble drugs. Omeprazole magnesium is a derivative of benzimidazole which belongs to the group of proton pump inhibitors that exhibits degradation in gastric acid with short biological life and variability in bioavailability. The drug degradation problem was overcome by the coating of pellets with enteric coating agents which disperse in the gastrointestinal tract more homogenously than single units with a rapid transit time. Pellets were compressed to reduce the tampering risk and transportation difficulty through the esophagus. The coating was done with the bottom spray technique. A batch of 5% concentration of binder optimized for a tablet affects the disintegration of the tablet. A cushioning agent was employed to optimize the acid resistance with a concentration of 12% and the release profile was depicted in pH 6.8 phosphate buffer followed by 0.1N HCl for 2 hours. The optimized batch was evaluated for acid resistance, similarity factor, SEM, dissolution, and stability studies which exhibited maximum resistance in gastric pH with abrupt release in duodenal pH because of the multi-particulate approach.

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.

Development and Formulation of Baicalin-loaded Self-nanoemulsifying Matrix Pellets

Development and Formulation of Baicalin-loaded Self-nanoemulsifying Matrix Pellets

FORMULATION DEVELOPMENT AND EVALUATION OF AQUEOUS POLYMER DISPERSIONS (PELLETS) FOR EXTENDED RELEASE DOSAGE FORMS OF GALANTAMINE HYDROBROMIDE

In this study, a novel approach for compression of matrix pellets into matrix tablets has been studied in an attempt to overcome the issues pertaining to rupture of polymer coat during compression of reservoir type pellets. Extended release matrix pellets were prepared by the extrusion/spheronization technique using commercially available aqueous dispersions of ethyl cellulose, acrylic polymers and sodium alginate at 10 %, 20 % and 30 % w/w levels. Galantamine Hydrobromide was used as the model drug and an in vitro release profile of 12 h was targeted. Tablets containing matrix pellets were prepared by the direct compression process. Acceptance Value, a pharmacopeial test, was applied to study the uniformity of drug distribution. Effect of compression force (2-6 kN), extrusion screen aperture size, diluent blend composition and pellet percentage on drug release and acceptance value were studied. As polymer is uniformly distributed within each pellet, the drug release pattern from uncompressed pellets was comparable to compressed tablets. The pellet segregated from the surface of the tablet was found to be flattened in the direction of applied compression force with minor deformities. In conclusion, matrix pellets can constitute an alternative approach to reservoir-type pellets in obtaining matrix tablets for extended delivery of drugs.

An Updated Overview on Mucoadhesive Buccal Drug Delivery System

Among the various routes of drug delivery, the oral route is an attractive site for the delivery of drugs. The main advantages of these formulations are: drug targeting, sustained release, increased permanence time in the buccal mucosa, increased bioavailability, and decreased potential adverse effects and maintains constant blood levels for extended period of time. The buccal cavity was found to be the most suitable and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery. Buccal mucosa has a tremendous availability, which leads to direct access to systemic circulation through the internal jugular vein bypasses the drug from hepatic first pass metabolism. The main disadvantage of this route is Limited absorption area- the total surface area of the membranes of the oral cavity available for drug absorption is 170 cm2 of which ~50 cm2 represents non-keratinized tissues, including buccal membrane, the barrier function of the skin changes from one site to the other and from one person to other person with age and large dose of drug are difficult to be administered. Melt granulation is emerging technique and this technique used to increase the dissolution rate of poorly water-soluble drugs. Tablet molding technique: Tablets produced by the molding technique are easier to scale up for industrial manufacture than lyophilisation technique. Hot melt extrusion of film method: Hot melt extrusion has been used for the manufacture of controlled release matrix tablets, pellets and granules, as well as oral disintegrating films.

Nanosuspension with improved saturated solubility and dissolution rate of cilostazol and effect of solidification on stability

The aim of the study was to formulate cilostazol containing nanosuspension by top-down wet milling method in order to increase the in vitro solubility and dissolution rate of this substance. The investigation of formulation parameters (emulsifier type, concentration, and combination of surface-active agents) on the milling efficiency was also brought into focus. The wet-milled and unmilled suspensions were applied onto solid carriers, and matrix pellets were prepared by extrusion/spheronization method. The reconstitution of nanoparticles from solid dosage forms was successful. Particle size reduction had a major impact on maximal thermodynamic solubility of cilostazol at pH = 1.2 and demonstrated a two times improvement compared to raw, unmilled surfactant dispersion. A significant effect on the highest dissolution rate constants at pH = 1.2 compared to raw, unmilled surfactant dispersion. Solid-state characterization of pulverized matrix pellets with differential scanning calorimetry and powder X-ray diffractometry indicated the transition of cilostazol Form A to amorphous form due to the extrusion process.

MANUFACTURE OF SPHERICAL GRANULES OF ISOSORBIDE DINITRATE WITH MODIFIED RELEASE

Objective: This study was aimed to obtain spherical matrix pellets of isosorbide dinitrate with different dissolution kinetics to create a multidosage medicinal form with controlled release of the active substance. Material and Method: Spherical matrix granules were obtained by extrusion-spherinization and coated with different amounts of polymer shell. Dissolution profiles of the obtained spheroids were compared with reference drug tablets. Result and Discussion: The results showed that the combination of spherical granules provides an isosorbide dinitrate release profile similar to the dissolution of Cardicet Retard tablets. The target dissolution profile is achieved using a combination of uncoated spherical granules and spheroids with a 10% film coating. The similarity coefficient (f2) is 73.6.

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.

Losartan potassium sustained release pellets with improved in vitro and in vivo performance

The aim of this study was to formulate and evaluate SR matrix pellets containing losartan potassium (LP) solid dispersion using extrusion–spheronization technique to minimize the fluctuation of its plasma concentration. LP solid dispersions were prepared by using different hydrophobic polymers at different weight ratios (0.5, 1, 2, and 5%). LP-Eudragit RS solid dispersion at 1:5 ratio resulted in slower drug release (only 20% of LP was released in about 8 h). Different concentrations of hydrophilic polymer, PEG 6000, were mixed with Avicel® PH 101 to prepare the LP SR matrix pellets containing solid dispersion using 32 full factorial design to evaluate the effects of formulation parameters on the pellets attributes. The magnitude of torque for the pellet wet masses and binder ratio were decreased significantly with increasing PEG 6000 concentration. LP sustained release pellet formula composed of 9.24% PEG 6000 and 8 × 10−9% PVP K30 solution was chosen as optimized formula. Pharmacokinetic studies revealed that calculated t max was 9.72 ± 2.22 h from the optimized sustained release pellets compared to 2.11 ± 0.49 h in case of Cozaar® immediate release tablet, indicating a slower release of the LP from pellets.

The Effect of Thermal-Treating on Drug Release from Sustained Release Alginate-Eudragit RS Matrices

Purpose: The main objective of the present study was to develop the colonic delivery system for 5-aminosalicylic acid (5-ASA) as an anti-inflammatory drug. Methods: Matrix pellets containing various proportions of alginate, calcium and Eudragit® RS were prepared by extrusion-spheronization technique. Thermal treatment was used to investigate the effect of the curing process on the surface morphology, mechanical and physicochemical properties and in vitro drug release profile of pellets. Based on the obtained results optimal formulations were selected to coating by the Eudragit® RS and subjected to a subsequent continuous dissolution test. Results: Image analysis and also scanning electron microscopy results proved acceptable morphology of the pellets. The fourier transform infrared spectroscopy and differential scanning calorimetry studies ruled out any interactions between the formulation’s components. Curing process did not alter the mechanical properties of pellets. The release rate of the drug from matrices was prolonged due to the decreased porosity of cured pellets. Furthermore, selected cured pellets which coated with Eudragit® RS, prevented undesired premature drug release. Conclusion: Formulation containing 17.5% calcium, 17.5% alginate, and a coating level of 10% demonstrated enhanced drug release so that provided resistance to acidic conditions, allowing complete drug release in alkaline pH, mimicking colonic environment. The slow and consistent drug release from this formulation could be used for treatment of a broader range of Inflammatory bowel disease (IBD) patients especially in whom colonic pH levels have been measured at lower than pH 7.0.

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.