Drug-polymer Ratio Research Articles

Drug Release Property of Poly 3-Hydroxybutyrate 4-Hydroxybutyrate (P34HB) as Drug-Eluting Coatings on Metal Coronary Stents.

Drug-eluting stents (DES) have become the main method of interventional therapy for coronary heart disease, because their drug coating can effectively reduce the incidence of restenosis after stent implantation. Biodegradable polymers for coatings are the latest development direction for coating polymers, because they can be degraded into small molecules in the human body. In this study, the polymer P34HB(P34HB-1:4HB% = 1 mol%, Mw: 225,000; P34HB-10:4HB% = 10 mol%, Mw: 182,000), the fourth generation of biodegradable Polyhydroxy alkanoates (PHAs), was coated on stents to evaluate the drug release properties of the DES. Both P34HB-1 and P34HB-10 coatings showed increased drug release rates, as the polymer concentrations were gradually increased from 8 mg/mL to 28 mg/mL. Both P34HB-1 and P34HB-10 coatings showed increased drug release rates as the drug polymer ratios were gradually changed from 1:10 to 1:2. The drug release rates of the P34HB-1 coatings became slower than P34HB-10, thus showing sustained drug release effects. The drug release rates of the P34HB-1 coatings decreased when Rates of solution flow increased, decreased when Focusing pressures decreased, and decreased when Mandrel moving speeds increased. P34HB-1 coatings prepared with CHCl3/NPA (10:1) mixed solvents had better controlled drug release rates compared to Firebird2®. The drug release rates of P34HB-1 coatings prepared with CHCl3 solutions decreased as the outer layer weights were increased from 0 to 800 μg. When the outer layer weights reached 800 μg, the drug release rates of P34HB-1 coatings were slower than Firebird2®. P34HB-1 coatings prepared with both CHCl3/NPA (10:1) mixed solvents and double layers had more effectively controlled drug release rates than P34HB-1 coatings prepared with only mixed solvents or double layers and these effects were far greater than Firebird2@; thus, P34HB-1 represents a latent polymer for DES.

Formulation and evaluation of polymeric microspheres of a poorly soluble drug celecoxib

The aim of this present work was to formulate microspheres of BCS Class II drug Celecoxib. The drug was identified by melting point study and FT-IR spectroscopy. Therapeutic success of a drug is greatly depended on its bioavailability. Majority of the recently discovered drugs shows poor solubility (BCS Class II) which decreases the bioavailability upon oral administration. Microspheres are a novel technique to circumvent this obstacle, which can increase bioavailability of drugs significantly. Polymeric microspheres with Polyvinylpyrrolidone and Eudragit L-100, prepared by Emulsion Solvent Diffusion and Evaporation technique, showed a range of drug release profile at intestinal pH 6.8. Different batches of microspheres were prepared by varying the drug-polymer ratio. Microparticulate systems like microspheres improve absorption which increases the bioavailability, ultimately leading to more efficient drug therapy. The microsphere system also provides protection to the gastric mucosa from GIT-irritant drugs thus decreasing toxic effects and sustained releases allows lower dosage frequency. Prepared microspheres were evaluated on various parameters like entrapment efficiency, %yield, particle size, scanning electron microscope analysis, and in-vitro drug release profile. Solid spherical microspheres were produced which showed good entrapment efficiency (43%-91%) and released 70-90% of the drug content in 10hrs.

Formulation and Evaluation of Hydroxypropylmethylcellulose-dicyclomine Microsponges for Colon Targeted Drug Delivery: In Vitro and In Vivo Evaluation.

The objective of the present study was to design novel colon targeted delivery of Dicyclomine Hydrochloride (DCH) microsponges. Microsponges (MS1-MS4) based on different ratios of Hydroxypropylmethylcellulose (HPMC) and DCH were prepared by quasi-emulsion solvent diffusion method. Micro-sponges were analyzed by determining percent yield, encapsulation efficiency, drug content, drug-polymer compatibility and thermal stability. Kinetic analysis of thermal stability data was done by Chang method, Friedman method and Broido method. In vitro dissolution study was carried out at pH 1.2, pH 6.8 and pH 7.4 at different time intervals. Results showed that there was no chemical interaction between DCH and HPMC in all microsponge formulations. Production yield, drug content and encapsulation efficiency were enhanced on increasing the drug-polymer ratio. Thermal stability of all the micro-sponges was greater than that of pure drug. In vitro drug release was decreased on increasing the polymer concentration at different pH levels. The newly prepared micro-sponges based on HPMC were confirmed as a promising means of colon-targeted delivery of DCH. An HPLC method was developed and validated for the bioequivalence study of newly designed microsponges. Pharmacokinetics parameters were calculated using the linear trapezoidal method after single oral administration of microsponges in white albino rabbits. Pharmacokinetics results indicate an enhancement in the value of t1/2, tmax, Cmax and AUC0-t of DCH in the microsponges as compared to standard DCH showing enhanced bioavailability of the drug after microsponges formation. The current study shows a new approach for colon-specific delivery of DCH based on microsponges.

Design and In Vitro Optimization of the Gastroretentive Microparticles Using Ethylcellulose and Eudragit

The biocompatible and bioadhesive polymers ethylcellulose and eudragit S100 are often used for controlled delivery of drugs in low pH conditions. Recent research focuses on designing and optimizing multiparticulate floating and bioadhesive systems using a central composite approach. Gastro-retentive floating microparticles of ethylcellulose and eudragit S100 containing itopride hydrochloride (ITH) were prepared using a solvent evaporation method. The impact of several process variables, including drug-polymer ratio, were studied on physicochemical parameters such as drug entrapment efficiency, particle size, bioadhesion, and release by employing a central composite design strategy. The experimental results were in good agreement with the predicted values of the optimization technique. The optimized microparticles had a 94.77 % drug entrapment efficiency, a particle size of 259.2 µm, 96.98 % drug release in simulated stomach fluid (pH 1.2) after 12 hours, and an 8-hour floating lag time. An accelerated stability analysis was conducted on the optimized formulation according to ICH criteria, and no significant changes in drug quantity were identified during storage. The microparticulate formulation containing ethylcellulose to eudragit S100 (in the ratio of 9:3) prepared by solvent evaporation technique displayed suitable pharmaceutical characteristics for controlled gastro retentive delivery of ITH. Furthermore, the results of the stability studies indicated that the developed formulation had not undergone any major changes under stress.

Molecular Dynamics Simulations of Essential Oil Ingredients Associated with Hyperbranched Polymer Drug Carriers.

Our work concerns the study of four candidate drug compounds of the terpenoid family, found as essential oil ingredients in species of the Greek endemic flora, namely carvacrol, p-cymene, γ-terpinene, and thymol, via the simulation method of molecular dynamics. Aquatic solutions of each compound, as well as a solution of all four together in realistic (experimental) proportions, are simulated at atmospheric pressure and 37 °C using an OPLS force field combined with TIP3P water. As verified, all four compounds exhibit a strong tendency to phase-separate, thereby calling for the use of carrier molecules as aids for the drug to circulate in the blood and enter the cells. Systems of two such carrier molecules, the hyperbranched poly(ethylene imine) (HBPEI) polyelectrolyte and hyperbranched polyglycerol (HPG), are examined in mixtures with carvacrol, the most abundant among the four compounds, at a range of concentrations, as well as with all four compounds present in natural proportions. Although a tendency of the terpenoids to cluster separately persists at high concentrations, promising association effects are observed for all drug–polymer ratios. HBPEI systems tend to form diffuse structures comprising small mixed clusters as well as freely floating polymer and essential oil molecules, a finding attributed to the polymer–polymer electrostatic repulsions, which here are only partially screened by the counterions. On the other hand, the electrically neutral HPG molecules cluster together with essential oil species to form a single nanodroplet. Currently, terpenoid–polymer clusters near lipid bilayer membranes are being studied to determine the propensity of the formed complexes to enter cell membranes.

Coarse-Grained Molecular Dynamics Simulations of Paclitaxel-Loaded Polymeric Micelles.

A continuous manufacturing technology based on coaxial turbulent jet in coflow was previously developed to produce paclitaxel-loaded polymeric micelles. Herein, coarse-grained molecular dynamics (CG-MD) simulations were implemented to better understand the effect of the material attributes (i.e., the drug-polymer ratio and the ethanol concentration) and process parameters (i.e., temperature) on the self-assembly process of polymeric micelles as well as to provide molecular details on micelle instability. An all-atom (AA) poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) polymer model was developed as the reference for parameterizing a coarse-grained (CG) model, and the AA polymer model was further validated with experimental glass transition temperature (Tg). The model transferability was verified by comparing structural properties between the AA and CG models. The CG model was further validated with experimental data, including micelle particle size measurements and drug encapsulation efficiency. Furthermore, the encapsulation of paclitaxel into the polymeric micelles was included in the simulations, taking into consideration the interactions between the paclitaxel and the polymers. The results from various points of view demonstrated a strong dependence of the shape of the micelles on the drug encapsulation, with micelles transitioning from spherical to ellipsoidal structures with an increasing paclitaxel amount. Simulation data were also used to identify the critical aggregation number (i.e., the number of polymer and drug molecules required for transition from one shape to another). Improved micellar structural stability was found with a larger micellar size and less solvent accessibility. Lastly, an evaluation was performed on the micellar dissociation free energy using a steered molecular dynamics simulation over a range of temperatures and ethanol concentrations. These simulations revealed that at higher ethanol and temperature conditions, micelles become destabilized, resulting in greater paclitaxel release. The increased drug release was determined to originate from the solvation of the hydrophobic core, which promoted micellar swelling and an associated reduction in hydrophobic interactions, leading to a loosely packed micellar structure.

Gastroretentive floating microspheres for the management hypertension based on drug combination of amlodipine /losartan

Background: Hypertension is one of the serious global health issues that affect millions of people and leads to cardiovascular damage if remain untreated. Various antihypertensive drugs have been developed but it is difficult to achieve better control of blood pressure by using mono-therapy so in this research work, combination therapy having sustained effect for the treatment of hypertension was developed. Method: Gastroretentive floating microspheres of amlodipine besylate and losartan potassium were formulated for the purpose of increasing the time of retention of drugs in the upper gastrointestinal tract and ultimately extend drug release. Eudragit RS100 was used as release controlling agent. The method adopted to prepare microspheres was solvent extraction. Formulated microspheres after that tested for assessing flow properties, buoyancy (%), percentage yield, drug release, surface morphology, by FTIR drug and polymer compatibility, size analysis and entrapment efficiency. Release kinetics on cumulative release data were applied. Results: It was observed from the findings that all the formulation remained buoyant in 1.2 pH buffer up to 12 hrs. It was also found that release of drug from formulation was prolonged which indicates sustained effect of dosage form. All the other results were satisfactory and it was also found that entrapment efficiency of formulation increased when concentration of polymer increased. On the basis of results, formulation 1 with 1:1 drug polymer ratio was selected as optimum formulation. Conclusion: It was concluded from the study that gastroretentive floating microspheres could be a one of best approach to extend the release of drug delivery system.

Synthesized nano particles of glimepiride via spray freezing into cryogenic liquid: characterization, antidiabetic activity, and bioavailability

The aim of this work was to formulate glimepiride (class II drug) which is characterized by low solubility and high permeability as nanostructured particles using a cryogenic technique with an aid of water-soluble polymer to improve its aqueous solubility and hence its bioavailability. 27 formula of glimepiride nano size particles were prepared by a spray freezing into cryogenic liquid (SCFL) using poly vinyl pyrrolidone K-30 (PVP K-30); that three drug polymer ratio (1:1, 1:2, and 1:3), with three different volumes of feeding solution (50, 100, 150 mL), at three flow rates (10, 20, and 30 mL/min). The prepared formulations were evaluated for production yield, particle size, zeta potential, drug content, release rate, in vivo hypoglycemic activity, and bioavailability. All prepared formulations showed high production yield and drug content ranged between 91.1 ± 3.4% and 94.3 ± 1.8% and 95.1 ± 2.8% and 97.1 ± 2.5%, respectively. The mean particles size was ranged between 280 ± 62 nm and 520 ± 30 nm. The results of in vitro release study revealed significant enhancement in the solubility of prepared formulations compared with the pure drug. It was found that optimal formula showed a significant reduction in blood glucose levels in diabetic rats, and 1.79-fold enhancements in oral bioavailability compared with market tablets. Nanoparticle prepared by SCFL method is an encouraging formula for improving the solubility and the bioavailability of glimepiride.

A Study on the Effects of Surfactant Concentration and Particle Size on Ethylcellulose Microspheres Containing Indinavir Sulphate

Microspheres containing indinavir sulfate were prepared by the emulsion solvent evaporation technique using surfactant sorbitan monooleate 80. The evaluation reports for Fourier-transform infrared spectroscopy and X-ray diffraction spectroscopy were taken to see whether the surfactant altered the physicochemical features of the produced microspheres. Scanning electron microscopy was used to observe the surface topography of the microspheres. When sorbitan monooleate 80 was employed at dissimilar concentrations, the sorbitan monooleate 80 microspheres had higher concentrations that resulted in smaller particle size as compared to the lower concentrations of sorbitan monooleate 80 microspheres, therefore, the faster release rate was observed by utilizing a higher concentration of sorbitan monooleate 80. The microspheres entrapped 71 % to 96 % of the drug and released it for up to 7 h. X-ray diffraction revealed a decrease in the crystallinity of the drug. Scanning electron microscopy analysis revealed the spherical and after dissolution detected porous structure of microspheres. The excellent fit release kinetics is accomplished with the zero-order, Higuchi plot followed by first-order, Hixson-Crowell and Korsmeyer-Peppas equations. As a result, the drug indinavir sulfate release rate was influenced by surfactant concentrations, drug-polymer ratio, particle size and the diffusion release mechanism.

Application of Box–Behnken Design and Desirability function in the Optimization of Aceclofenac-Loaded Micropsonges for Topical Application

Background: The aim of the present investigation was to develop optimized Aceclofenac-loaded microsponges using Box-Behnken design (BBD) and desirability function. Material and Method: Aceclofenac-loaded microsponges were developed using ethyl cellulose, ethanol and polyvinyl alcohol (PVA). Initially, a trial batch was developed using quasi-emulsion solvent diffusion method, and by optimizing the drug-polymer ratio. A 3-level, 3-factor BBD was used to investigate the effect of PVA, ethanol and stirring speed on particle size and entrapment efficiency (EE). The models used for the optimization were analyzed through ANOVA and diagnostic plots. Finally, the desirability function was used for the selection of optimized formulation composition. Results: A drug-polymer ratio of 1.5:1 was taken as optimized ratio for all the formulations. The developed microsponges were of the spherical shape having size and %EE in the range of 22.54±2.85 µm to 49.08±5.01 µm and 70.57±4.19% to 86.43±2.58 %, respectively. The amounts of PVA, ethanol and stirring speed were noted to have a significant impact on particle size and %EE. Finally, an optimized formulation (size-22.69 and %EE-86.42) was developed with a desirability value of 0.9967. Conclusion: The BBD is a valuable tool for the development of optimized microsponges with desired properties.

Stability Testing of Amoxicillin Nano-suspension as Promising Tool for Drug Delivery System

While nano-suspension amoxicillin is one of the approaches for improving dissolution rate of amoxicillinan antibiotic used widely. Stabilizing these nanodosage forms is always a challenge. The present study utilizes nanoprecipitation solvent evaporation technique for preparation of amoxicillin nanoparticles andproposed stability study approach of the same. The methodology was based on investigating stability of amoxicillin nano suspension in vitro, the optimized drug(polymer ratio re-formulated into nano-suspensions) and we compared our results with marketed suspensions. Samples were initially characterized and then subjected to stability testing at ambient temperature and relative humidity up to 6 months assayed using a validated HPLC method. During initial characterization, increase in saturation solubility and dissolution rate observed in all samples. During stability testing, there was gradual decrease in saturation solubility and dissolution rate of the samples, over the period of 3 months. This study considers long-term isothermal measurements, consistent with short-term non-isothermal (accelerating) measurements, providing predictive model to calculate the isothermal degradation periods. As per our results, we agree with the possibility to calculate the value of kinetic constants based on a fixed degradation limit, regardless of the shape of the curve. The accuracy of the prediction would be assessed by comparison of estimated shelf life versus data coming from traditional stability studies.

Long-acting injectable donepezil microspheres: Formulation development and evaluation

Novel formulations of donepezil (DNP)-loaded microspheres based on a bio-degradable polymer of poly(lactic-co-glycolic acid) (PLGA) with a one-month duration of effect were developed, aimed at reducing dosing frequency and adverse effects and improving patient adherence. The spherical and monodispersed DNP-loaded microspheres were precisely fabricated by the Inventage Lab Precision Particle Fabrication method (IVL-PPFM®) based on micro-electromechanical systems (MEMS) and microfluidic technology. The types of polymers and end-groups, the drug/polymer ratio (DPR), and the routes of administration for DNP were studied to ensure an effective concentration and desired duration. Laser-light particle size analysis and scanning electron microscopy were used to characterization. Also, non-clinical animal models of beagle dogs are used to optimize DNP formulations and evaluate their pharmacokinetic properties. The PK results showed that the DPR was a critical factor in determining the exposure level and duration of DNR release. Furthermore, the lactide ratio, which varied depending upon the type of polymer, determined the hydrophobic interaction and was also an important factor affecting the desired DNP release. Since DNP shows a large inter-species variation between dogs and humans, PK modeling and simulation of the reference drug (i.e., Aricept®) and DNP-loaded microspheres were used for formulation development to overcome and interpret these variations. In addition, the developed PK model was extrapolated to humans using the estimated PK parameter and published clinical pharmacology data for DNP. The predicted PK profile of the DNP-loaded microsphere in humans showed that the formulation with PLGA 7525A and the DPR of 1/9 could maintain drug concentration for a month and could control initial burst release. The data obtained from the study could be used as scientific evidence for decision-making in future formulation development.

Optimized Rivastigmine Nanoparticles Coated with Eudragit for Intranasal Application to Brain Delivery: Evaluation and Nasal Ciliotoxicity Studies.

Rivastigmine, a reversible cholinesterase inhibitor, is frequently indicated in the management of demented conditions associated with Alzheimer disease. The major hurdle of delivering this drug through the oral route is its poor bioavailability, which prompted the development of novel delivery approaches for improved efficacy. Due to numerous beneficial properties associated with nanocarriers in the drug delivery system, rivastigmine nanoparticles were fabricated to be administer through the intranasal route. During the development of the nanoparticles, preliminary optimization of processing and formulation parameters was done by the design of an experimental approach. The drug–polymer ratio, stirrer speed, and crosslinking time were fixed as independent variables, to analyze the effect on the entrapment efficiency (% EE) and in vitro drug release of the drug. The formulation (D8) obtained from 23 full factorial designs was further coated using Eudragit EPO to extend the release pattern of the entrapped drug. Furthermore, the 1:1 ratio of core to polymer depicted spherical particle size of ~175 nm, % EE of 64.83%, 97.59% cumulative drug release, and higher flux (40.39 ± 3.52 µg.h/cm2). Finally, the intranasal ciliotoxicity study on sheep nasal mucosa revealed that the exposure of developed nanoparticles was similar to the negative control group, while destruction of normal architecture was noticed in the positive control test group. Overall, from the in vitro results it could be summarized that the optimization of nanoparticles’ formulation of rivastigmine for intranasal application would be retained at the application site for a prolonged duration to release the entrapped drug without producing any local toxicity at the mucosal region.

Freeze-Drying Ethylcellulose Microparticles Loaded with Etoposide for In Vitro Fast Dissolution and In Vitro Cytotoxicity against Cancer Cell Types, MCF-7 and Caco-2

The aim of this study was to improve the solubility of etoposide–ethylcellulose (ET–ETO) microparticles using the freeze-drying technique. Ethylcellulose (EC) microparticles loaded with etoposide (ETO) were prepared with different drug–polymer molar ratios of 1:1, 1:3, 1:6, and 1:20 by the solvent evaporation method. The size of the prepared microparticles was 0.088 µm. The results showed that the amount of ETO encapsulated into the microparticles was 387.3, 365.0, 350.0, and 250 µg/50 mg microparticles for microparticles with drug–polymer ratios of 1:1, 1:3, 1:6, and 1:20, respectively. The FT-IR spectra showed no chemical interaction between ETO and the polymer in the solid state. The results obtained from the dissolution experiment showed that the freeze-dried microparticles were stable in 0.1 N HCl (gastric pH) for 2 h. At pH 7.4, the ETO release was 60 to 70% within the first 15 min and approximately 100% within 30 min. Results from the application of different dissolution models showed that the equations that best fit the dissolution data for the ET–ETO microparticles at pH 7.4 were the Higuchi and Peppas model equations. The in vitro cytotoxicity assay of free ETO and freeze-dried microspheres prepared in this study with a drug–polymer ratio of 1:1 was performed in two mammalian cancer cell lines, MCF-7 (for bone cancer of the mammary organ) and Caco-2 (for mammalian epithelial colorectal adenocarcinoma). The results showed that the half-maximal inhibitory concentrations (IC50 values) for ETO and freeze-dried ET–ETO microparticles were 18.6 µM and 27.1 µM, respectively. In conclusion, freeze-dried ET–ETO is a promising formulation for developing a fast-dissolving form of ETO with a significant antiproliferative activity against the tested cell lines used in this study. It is a promising formulation for local duodenal area targeting.

CENTRAL COMPOSITE DESIGN FOR FORMULATION AND OPTIMIZATION OF LONG-ACTING INJECTABLE (LAI) MICROSPHERES OF PALIPERIDONE PALMITATE

Objective: The aim of the present study was to optimize long-acting injectable (LAI) microspheres of Paliperidone palmitate (PP) for treatment of schizophrenia using face-centered central composite design (FC-CCD). Methods: In this study, poly lactic-co-glycolic acid (PLGA) based LAI microspheres of paliperidone palmitate (PP) were formulated by using FC-CCD. LAI microspheres were developed by using oil in water (O/W) emulsion solvent evaporation technique. On the basis of preliminary trials, FC-CCD was employed to check effect of independent variables such as drug polymer ratio (X1), homogenization speed (X2) and rate of addition (X3). While mean particle size (Y1), drug loading (Y2), entrapment efficiency (Y3), burst release (Y4), and drug release on day 60 (Y5) were considered as dependent variables and statistically evaluation performed by using design expert 12 software. Morphology of prepared microspheres was studied by using the scanning electron microscopy (SEM) technique, while particle size was analyzed by laser diffraction technique. In vitro drug release studies were performed using a controlled temperature shaking water bath apparatus. Fourier transforms infrared spectroscopy (FTIR) and differential scanning calorimetric (DSC) study were performed to analyze any changes in crystal behavior or to detect any chemical bonding between ingredients. 13C NMR and 1H NMR techniques were used to analyze end-capping and monomer ratio in developed microspheres. Results: The factorial batches mean particle size was found to be 38 µm to 104 µm and drug loading were found between 27.2 % to 47.2%. Mathematical modelling of drug release kinetics revealed that near zero-order drug release of checkpoint formulations. Endcap analysis and molar ratio of formulated microspheres were found to be ester end cap and ~75:25, respectively. Morphologically all the prepared samples were found to be spherical in shape and smooth surface. FTIR data showed no significant interactions occurred between drug and excipients. The actual responses of checkpoint formulations were observed within 5% variation of predicted values. Conclusion: The prepared microspheres showed promising results of morphology, particle size, drug loading, entrapment efficiency, burst release and drug release on day 60. The successful predictive designs models were achieved from employed FC-CCD.

FORMULATION AND EVALUATION OF DRUG RELEASE PROFILE OF HYDROPHILIC POLYMER BASED INDOMETHACIN PROLONG RELEASE MATRIX TABLETS

An oral modied release dosage forms have always been more effective therapeutic alternative to conventional dosage forms. The present invention is directed to a modied release pharmaceutical composition of indomethacin by using hydrophilic release retardant polymers like HPMC K15M, Na CMC alone or in combination. Matrix embedded prolong release tablet formulations of Indomethacin were prepared by wet granulation technique and evaluated for tablet properties such as the thickness, hardness, friability, weight variation, drug content, drug release kinetics and in vitro release studies. The inuence of drug polymer ratio on drug release was studied by dissolution test. The FTIR studies showed no interactions among drug and polymers. The tablets formulation (F7 and F8) containing combined polymers of HPMC K15M and Na CMC resulted in slower drug release rate form the matrix. So, it can be concluded that Indomethacin prolong release tablets using HPMC K15M and Na CMC as the retardant has successfully extended the release of indomethacin from its formulations. The mixing of two cellulose polymers, ionic and non-ionic, for the formulation of hydrophilic matrices, resulted in a valuable decrease in drug release rate. All the formulations showed KorsmeyerPeppa’s model as a best t.

Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement.

The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO2) processing for the preparation of simvastatin (SIM) solid dispersions (SDs) in Soluplus® (SOL) at temperatures below polymer’s glass transition. The SIM content in the SDs experimental design was kept at 10, 20 and 30% to study the effect of the drug–polymer ratio on the successful preparation of SDs. The SIM–SOL formulations, physical mixtures (PMs) and SDs were evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and dissolution studies. The scCO2 processing conditions and drug–polymer ratio were found to influence the physicochemical properties of the drug in formulated SDs. SIM is a highly crystalline drug; however, physicochemical characterisation carried out by SEM, DSC, and XRD demonstrated the presence of SIM in amorphous nature within the SDs. The SIM–SOL SDs showed enhanced drug dissolution rates, with 100% being released within 45 min. Moreover, the drug dissolution from SDs was faster and higher in comparison to PMs. In conclusion, this study shows that SIM–SOL dispersions can be successfully prepared using a solvent-free supercritical fluid process to enhance dissolution rate of the drug.

Gas anti-solvent coprecipitation of pyrazinamide–PVP composite particles from mixed organic solvents using supercritical CO2: Effect of process parameters

This paper focuses on coprecipitation of pyrazinamide (PZA) with polyvinylpyrrolidone (PVP) using gas antisolvent (GAS) process. Solutions of PZA/polymer in solvent mixtures (acetone and ethanol) with an overall concentration of 20 mg/ml were prepared. The process parameters: pressure, temperature, antisolvent addition rate, solvent composition, and polymer-drug ratio were manipulated to simplify the obtainability of controlled morphology and particle size distribution. Solvent-free particles with reduced crystallinity were precipitated having mean sizes between 311 and 1474 nm. Furthermore, the operating pressure and polymer-drug ratio stood as key parameters affecting the PVP/PZA particle size. The knowledge of the particle characteristics was the main objective in order to identify the crystalline phase and physicochemical properties of the final product. The drug release analyses revealed that by tuning the operating parameters, dissolution rate of PVP/PZA particles could reach near 90%, which was 2.5 times faster than the unprocessed PZA and thus facilitated drug assimilation through the organism.

Formulation and Evaluation of Sustained Release Ibuprofen Matrix Tablets Using Starch from Maize Genotypes as Polymer

Abstract Objective: Maize plants have been genetically engineered to produce genotypes with agriculturally desirable traits such as high starch content, pest resistance and increased nutritional value. Maize starch has been widely used as an excipient in pharmaceutical formulations. This study aims to produce sustained release ibuprofen tablets using starch obtained from different maize genotypes as polymers. Methods: Ibuprofen matrix tablets were prepared with the starches isolated from the maize genotypes and the unmodified plant. The mechanical properties of the tablets were evaluated using the crushing strength (CS), friability (FR) and CSFR. A 32 factorial design was applied using the time taken for 50 % (T50) and 90 % (T90) drug release as dependent variables while the polymer-drug ratio and polymer types were the independent variables. Results: The CSFR was significantly higher (p<0.05) in tablets formulated with the starches obtained from the modified cultivars. Drug release for all the formulations fitted the Higuchi model while the mechanism of release was generally by super case transport. The polymer-drug ratio and polymer type strongly interacted to increase the dissolution times (T50 and T90) and CSFR. Starches isolated from the genetically modified cultivars provided a more sustained release of ibuprofen from the tablet matrix through erosion and polymer relaxation. Conclusion: The results indicate that the genetic modification of maize can quantitatively affect the drug release modifying effects of maize starch in drug formulation.

Formulation and evaluation of orally disintegrating tablet containing taste masked mirtazapine

Objective: This study aims to prepare the taste-masked granules of Mirtazapine by mass extrusion technique and formulate it into an oral dispersible tablet using different super disintegrates. Methods: Taste masked granules of mirtazapine were prepared by mass extrusion technique using Eudragit EPO in different ratios. The drug-polymer ratio was optimized based on the percent drug release in SSF and SGF. Taste masking efficacy of drug-polymer complex was determined by developing the bitterness threshold value of Mirtazapine. The selected drug-polymer complex was formulated into an oro-dispersible tablet by direct compression method. A randomized design was used to investigate individual effect of three different super disintegrates each in different concentrations. Ten formulations were developed including a controlled formulation without the addition of superdisintegrants. A comparative study was done based on various pre-compression and post-compression parameters. Results: Eudragit EPO was able to mask the bitter taste of Mirtazapine effectively in 1:2 ratio by mass extrusion method. The minimum disintegration time and wetting time was found to be 13.6±2.7 and 18.13±0.24 seconds with the formulation containing crospovidone 5% (F9). It was found that the wetting time and disintegration time followed the order SSG>CCS>CPV. The selected best formulation was subjected to an incompatibility study design. The IR spectrum showed that all the excipients were chemically compatible. Conclusion: Thus, in this study unpalatable taste of Mirtazapine was masked using Eudragit EPO polymer by mass extrusion technique, and superdisintegrants were added to prepare orally disintegrating tablets of Mirtazapine. This research work suggests a rapid, simple and cost effective method for formulating Mirtazapine ODT.