Differences In Release Profiles Research Articles

Tablet Geometry Effect on the Drug Release Profile from a Hydrogel-Based Drug Delivery System.

In order to achieve the optimal level of effectiveness and safety of drugs, it is necessary to control the drug release rate. Therefore, it is important to discover the factors affecting release profile from a drug delivery system. Geometry is one of these effective factors for a tablet-shaped drug delivery system. In this study, an attempt has been made to answer a general question of how the geometry of a tablet can affect the drug release profile. For this purpose, the drug release process of theophylline from two hundred HPMC-based tablets, which are categorized into eight groups of common geometries in the production of oral tablets, was simulated using finite element analysis. The analysis of the results of these simulations was carried out using statistical methods including partial least squares regression and ANOVA tests. The results showed that it is possible to predict the drug release profile by knowing the geometry type and dimensions of a tablet without performing numerous dissolution tests. Another result was that, although in many previous studies the difference in the drug release profile from several tablets with different geometries was interpreted only by variables related to the surface, the results showed that regardless of the type of geometry and its dimensions, it is not possible to have an accurate prediction of the drug release profile. Also, the results showed that without any change in the dose of the drug and the ingredients of the tablet and only because of the difference in geometry type, the tablets significantly differ in release profile. This occurred in such a way that, for example, the release time of the entire drug mass from two tablets with the same mass and materials but different geometries can be different by about seven times.

Major difference in particle size, minor difference in release profile: a case study of solid lipid nanoparticles

Solid lipid nanoparticles (SLN) have been widely used in a variety of drug delivery routes, which have the outstanding advantage of controlled drug release. The release of SLN is dominated by many factors, among which the particle size of SLN is a critical one. The aim of this project was to explore the relationship between drug release profile and particle size of SLN. SLN were synthesized via the hot high-pressure homogenization (HPH) method, budesonide (BUD) was used as the model drug, and BUD-SLN1–BUD-SLN4 with increasing particle size was obtained, i.e. 120, 240, 360, and 480 nm. The prepared SLN has good encapsulation efficiency, drug loading capacity, and stability. In vitro release behavior studies showed that the cumulative release of BUD-SLN in Tris-Maleate (Tris-M) media was negligible, while that in Tris-M plus pancreatin media or Tris-M-ethanol media obeyed Ritger-Peppas model or first-order kinetic model, respectively. Noticeably, the release behavior of SLN was to some extent related to the average particle size of SLN, but the correlation was insignificant when the intersection degree of particle size distribution was great. This study provides a new idea for the understanding of in vitro release of SLN and has a certain referencing value for the research and development of novel nanomedicines.

FORMULATION DEVELOPMENT AND EVALUATION OF CHRONOMODULATED DRUG DELIVERY SYSTEM BY ZAFIRLUKAST

Objective: The main objective of the present study was to formulate and evaluate a time-controlled single-unit oral pulsatile drug delivery system containing Zafirlukast for the prevention of nocturnal asthma attacks. To provide time-scheduled drug release for Asthma disease. It is used for preventing asthmatic attacks at early morning. Pulsatile release dosage form is increasing patient compliance by reducing the dosing frequency, especially in the early morning.
 Methods: Core tablets were prepared by incorporating different concentrations of natural and synthetic super disintegrants. Drug-containing core tablets (ZC1-ZC15) with different compositions of natural super disintegrants (Plantago ovata seed powder, Locust bean gum) synthetic super disintegrants (Sodium starch glycolate (SSG), Cross carmellose sodium (CCS), Crospovidone (CP)) were prepared by direct compression technique. The core tablets were subjected to pre-formulation, physicochemical and In vitro drug release studies. The fast disintegrating core tablet formulation was selected and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic polymers Eudragit RS100, Eudragit RL 100, Ethylcellulose and hydrophilic polymers Hydroxypropyl methylcellulose K4M, K100M. The optimized formulation was selected and quantified based on in vitro drug release profile in simulated gastric and intestinal fluids.
 Results: The pre and post-compression parameters of tablets were also found to be within limits. Formulation ZC5 with 16 mg of Locust bean gum showed the least disintegrating time, i.e., 22.13 sec, and was selected as the best immediate release core tablet. The press-coated tablet formulation P8 having 62.5 mg Eudragit RS100 and 62.5 mg of HPMC K4M in ratio 1:1 over the core tablet ZC5 showed rapid and drug release nearly after 4 h lag time and 98.86 % up to 12 h. Accelerated stability studies of the optimized formulation P8 indicated no significant difference in release profile after 3 mo.
 Conclusion: The in vitro dissolution study showed that lag time before drug release was highly affected by the coating amount level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques.

Electrospun Membranes as a Porous Barrier for Molecular Transport: Membrane Characterization and Release Assessment.

Electrospun nanofibers have been extensively studied for encapsulated drugs releasing from the inside of the fiber matrix, but have been barely looked at for their potential to control release as a semi-permeable membrane. This study investigated molecular transport behaviors across nanofiber membranes with different micro-structure sizes and compositions. Four types of membranes were made by 5% and 10% poly (ε-caprolactone) (PCL) solutions electro-spun with or without 50 nm calcium carbonate (CaCO3) nanoparticles. The membranes were tested for thickness, fiber diameter, pore size, porosity, tensile strength and elongation, contact angle of water and their impacts on molecular transport behaviors. The presence of the CaCO3 nanoparticles made the 5% membranes stronger and stiffer but the 10% membranes weaker and less stiff due to the different (covering or embedded) locations of the nanoparticles with the corresponding fibers. Solute transport studies using caffeine as the model drug found the 5% membranes further retarded release from the 10% membranes, regardless of only half the amount of material being used for synthesis. The addition of CaCO3 nanoparticles aided the water permeation process and accelerated initial transports. The difference in release profiles between 5% and 10% membranes suggests different release mechanisms, with membrane-permeability dominated release for 5% PCL membranes and solute-concentration-gradient dominated release for 10% PCL membranes.

FORMULATION AND EVALUATION OF PULSATILE DRUG DELIVERY SYSTEM OF SALBUTAMOL SULFATE FOR THE CHRONOTHERAPY OF ASTHMA

Objective: The main objective of the present study was to design and evaluate a time-controlled single unit oral pulsatile drug delivery system containing salbutamol sulfate for the prevention of nocturnal asthma attacks.Methods: Drug containing core tablets (C1-C10) with different composition of superdisintegrants such as sodium starch glycolate, croscarmellose sodium, and crospovidone were prepared by direct compression technique. The fast disintegrating core tablet formulation was selected, and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic and hydrophilic polymers: Ethylcellulose-20 (EC-20), hydroxypropyl methylcellulose K4M, and low substituted hydroxypropyl cellulose (L-HPC LH11). The coating polymers were selected and quantified based on in vitro lag time and drug release profile in simulated gastric and intestinal fluids.Results: Formulation C10 with 7.5% crospovidone showed least disintegrating time, i.e., 0.31 min and was selected as the best immediate release core tablet. The press-coated tablet formulation P11 having 360 mg barrier layer of EC-20 and L-HPC LH11 in ratio 14:1 over the core tablet C10 showed rapid and complete drug release nearly after 6 h lag time. Accelerated stability studies of the optimized formulation P11 indicated no significant difference in release profile after a period of 6 months.Conclusion: The in vitro dissolution study showed that lag time before drug release was highly affected by the coating level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques.

Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation

Objective: Novel antibiotic Ramizol® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing.Significance: The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance.Methods: Ramizol® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague–Dawley rats.Results: Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague–Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in Tmax and T1/2 when compared to the oral and IV routes.Conclusions: Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol®. This formulation will allow further development of Ramizol® for systemic infection eradication.

In vitro release testing method development for ophthalmic ointments

It is essential as well as challenging to develop a reliable in vitro release testing method for determining whether differences in release profiles exist between qualitatively and quantitatively equivalent ophthalmic ointment formulations. There is a lack of regulatory guidance on in vitro release testing methods for ophthalmic formulations. Three different in vitro release testing methods 1) USP apparatus 4 with semisolid adapters; 2) USP apparatus 2 with enhancer cells; and 3) Franz diffusion cells were investigated. Qualitatively and quantitatively equivalent ointments were prepared via hot melting and simple mixing methods using four different sources of excipients (i.e. white petrolatum). The ointment formulations were characterized for content uniformity, particle size, and rheological parameters. All the formulations showed adequate content uniformity and similar particle size. The ointments prepared via the hot melting processes showed higher rheological parameters, as did the ointments prepared using ‘white’ petrolatum that exhibited a yellowish color. The three in vitro release testing methods were compared and evaluated for reproducibility, discriminatory capability, and correlation with the rheological parameters. Compared with the compendial methods, the non-compendial method (Franz diffusion cells) showed poorer reproducibility. All three methods possessed the ability to discriminate between the ophthalmic ointments with manufacturing differences. However, the USP apparatus 4 method displayed the largest margin of discrimination between the release profiles of the different ophthalmic ointments. In addition, the in vitro release rate obtained using the USP apparatus 4 method showed the strongest logarithmic linear correlation with the rheological parameters (Power law consistency index (K value) and crossover modulus) compared to the other two methods.

OP.4C.10] CLINICALLY IMPORTANT DIFFERENCES IN SYSTOLIC AMBULATORY BLOOD PRESSURE IN PATIENTS SWITCHED BETWEEN ALTERNATE NIFEDIPINE OSMOTIC DELIVERY FORMULATIONS

Objective: Anecdotal evidence suggested clinically important systolic blood pressure (SBP) differences occurred in our patients whose nifedipine was being switched by pharmacies between AdN (Adalat XL – a formulation providing zero order release from the GastroIntestinal Therapeutic System - GITS) and MyN (Mylan-nifedipine ER - a formulation providing a delayed first-order release from the Osmotic Release Oral System - OROS). In vitro dissolution studies showed greater lag time to initial release from MyN and declining release at end of dosing interval. The objective of this study was to use Ambulatory Blood Pressure Monitoring (ABPM) to examine whether differences in overall effectiveness and duration of action exist between these two nifedipine formulations. Design and method: A randomized cross-over trial studied 20 patients receiving daily morning AdN vs. MyN 60 mg. After each 2-week period, 24-h ABPM was done. SBP data for 24 h and last 8 h (22:00 - 06:00 h) were examined using a Generalized Additive Mixed Model (GAMM). The software (R) used 2560 data points to model SBP population curves and compare them statistically. Results: GAMM of SBP over time showed MyN mean ± SE SBP was 2.59 ± 1.09 mmHg higher for 24 h (p = 0.0173) and 4.18 ± 1.6 mmHg higher for last 8 h (p = 0.0098). Mean 24-h SBP was > = 2 mmHg higher, while taking MyN in 50% of patients while SBP for last 8 h ranged as high as 18 mmHg higher while taking MyN.Conclusions: Clinically meaningful differences in SBP were seen in a cohort of patients when taking MyN compared to when they were taking AdN. This was likely based on differences in release profiles. For nifedipine, a potent vasodilator with a steep dose-response relationship and a 2-hour half-life, differences in timing and/or extent of delivery over as little as 6 h could allow clinically important changes in SBP. These data support the conclusion that formulations using differing release technologies are not suitable for bioequivalence testing. Undisclosed switching of nifedipine formulations by pharmacies can lead to an undesirable increase in variability in BP control.

Formulation and Evaluation of Cinitapride Controlled Release Tablets

The present study aimed at Formulation Development and Evaluation of controlled release tablets of Cinitapride for the treatment of ulcer. Cinitapride is a gastroprokinetic agent and antiulcer agent of the benzamide class. It act as an agonist of the 5-HT1 and 5-HT4 receptors and an antagonist of the 5-HT2 receptors. It is used in the treatment of gastrointestinal disorders associated with motility disturbances such as gastro esophageal reflux disease, non-ulcer dyspepsia and delayed gastric emptying. The matrix tablets of Cinitapride were prepared using wet granulation. Physical characterization of tablet and powder blends used to form the matrix tablet was under taken using a range of experimental techniques. Granules were evaluated for Bulk density, Tapped density, Compressibility index and Hausner's ratio. Tablets were tested for weight variation, hardness, thickness and friability as per official procedure. The tablets were evaluated for in-vitro drug release profile. Dissolution studies of Cinitapride controlled release tablets in media with different dissolution media 0.1N HCl, Phosphate buffer pH (6.8) as per US Pharmacopoeia. The dissolution data revealed that the ratio of polymers is very important to achieve a optimum formulation. The formulation of Cinitapride CR tablets shown that formulation F23 with Methocel K100M (20%) shown good drug release profile. Formulation F23, shown similar dissolution profile when compared with the marketed product (Cintapro). Stability study of the formulation F23 indicated no significant difference in release profile after a period of 3 months.

Controlled release of proteins from polymeric microparticles based on electrostatic interactions

Event Abstract Back to Event Controlled release of proteins from polymeric microparticles based on electrostatic interactions Vida Rahmani1 and Heather Sheardown1, 2 1 McMaster University, Chemical Engineering, Canada 2 McMaster University, School of Biomedical Engineering, Canada Introduction: The focus of this work is the development of new hydrogel microparticles that offer controlled release of protein drugs through modification of the absolute charge of the hydrogel network. An appropriate protein delivery vehicle can be developed by understanding relationships between release profiles of proteins and their net charge and molecular weight and by adapting the vehicle accordingly. Alginate, an anionic and non-toxic polymer, forms gels with multivalent cations under mild processing conditions[1]. Positively charged proteins also interact with alginate to form polyelectrolyte complexes, generating novel drug delivery systems. In addition, grafting amine groups on alginate leads to synthesis of positively modified alginate[2]. Materials and Methods: Lysozyme/calcium-alginate complexes were prepared by mixing solutions of alginate and lysozyme/calcium at room temperature. The concentration of the lysozyme and calcium solutions were calculated to achieve different molar charge mixing ratios and a constant total concentration of charge. Cationically modified alginate was prepared by grafting amine groups onto the alginate backbone using aqueous carbodiimide chemistry. Alginate and amine modified alginate microparticles were prepared by emulsification and external gelation methods. Model proteins with a variety of net charges and molecular weights were used in protein loading and release studies (done at 37°C). Protein amounts were quantified using the Bradford assay. Results and Discussion: Protein loading studies (Figure 1) show that protein charge and molecular weight have a significant effect on protein loading amounts. Higher protein loading amounts were observed with lysozyme and insulin, as a result of the positive nature of lysozyme and small size of insulin. While the electronegativity and large molecular weight of fibrinogen both are limiting factors inhibiting its diffusion into the alginate particles. The release profiles (Figure 2) show that while absence of sufficient calcium leads to formation of loose networks and burst release (Lys100-Ca0 and Lys75-Ca25), electrostatic interactions play a dominant role in the diffusive properties of lysozyme. As seen from release profiles of Lys50-Ca50 and Lys25-Ca75, proteins could serve as physical crosslinkers for the alginate matrix and these crosslinks have a slower degradation rate in the presence of monovalent ions compared to crosslinks formed by calcium ions (Lys0-Ca100). Conclusion: The difference in release profiles of the proteins is a result of electrostatic interactions between the protein and polymeric microparticles and also the molecular weight of the protein. Electrostatic interactions between hydrogels and proteins can be optimized to control the protein release by understanding the developed relationships between the release profiles of proteins and their net charge and molecular weight. We would like to thank NSERC for grant funding

Keratin hydrogel carrier system for simultaneous delivery of exogenous growth factors and muscle progenitor cells.

Ideal material characteristics for tissue engineering or regenerative medicine approaches to volumetric muscle loss (VML) include the ability to deliver cells, growth factors, and molecules that support tissue formation from a system with a tunable degradation profile. Two different types of human hair-derived keratins were tested as options to fulfill these VML design requirements: (1) oxidatively extracted keratin (keratose) characterized by a lack of covalent crosslinking between cysteine residues, and (2) reductively extracted keratin (kerateine) characterized by disulfide crosslinks. Human skeletal muscle myoblasts cultured on coatings of both types of keratin had increased numbers of multinucleated cells compared to collagen or Matrigel(TM) and adhesion levels greater than collagen. Rheology showed elastic moduli from 10(2) to 10(5) Pa and viscous moduli from 10(1) to 10(4) Pa depending on gel concentration and keratin type. Kerateine and keratose showed differing rates of degradation due to the presence or absence of disulfide crosslinks, which likely contributed to observed differences in release profiles of several growth factors. In vivo testing in a subcutaneous mouse model showed that keratose hydrogels can be used to deliver mouse muscle progenitor cells and growth factors. Histological assessment showed minimal inflammatory responses and an increase in markers of muscle formation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 864-879, 2016.

Formulation and Evaluation of Controlled Release Matrix Tablets of Sotalol

The present study aimed at Formulation Development and Evaluation of controlled release tablets for the programmed release of sotalol hydrochloride for the treatment of Arrhythmia. The matrix tablets of sotalol hydrochloride were prepared using wet granulation. Physical characterization of tablet and powder blends used to form the matrix tablet was under taken using a range of experimental techniques. Instacoat EN II was used as enteric coat polymer for coating the matrix tablet. Dissolution studies of sotalol hydrochloride controlled release tablets in media with different dissolution media 0.1 N HCl, pH (7.4) as per US Pharmacopeia. The study showed that, drug release in 2hr was highly affected by the coating level. The dissolution data revealed that the % of coating, ratio of polymers and concentration of Compritol 888 ATO are very important to achieve a optimum formulation. Dissolution shows that the drug release from F12 is very similar to Marketed brand (Sotalar). Stability study of the optimized formulation indicates no significant difference in release profile after a period of one month.

Synthesis and characterization of biocompatible polyurethanes for controlled release of hydrophobic and hydrophilic drugs

Design of biocompatible and biodegradable polymer systems for sustained and controlled release of bioactive agents is critical for numerous biomedical applications. Here, we designed, synthesized, and characterized four polyurethane carrier systems for controlled release of model drugs. These polyurethanes are biocompatible and biodegradable because they consist of biocompatible poly(ethylene glycol) or poly(caprolactone diol) as soft segment, linear aliphatic hexamethylene diisocyanate or symmetrical aliphatic cyclic dicyclohexylmethane-4,4′-diisocyanate as hard segment, and biodegradable urethane linkage. They were characterized with Fourier transform infrared spectroscopy, atomic force microscope, and differential scanning calorimetry, whereas their degradation behaviors were investigated in both phosphate buffered saline and enzymatic solutions. By tuning polyurethane segments, different release profiles of hydrophobic and hydrophilic drugs were obtained in the absence and presence of enzymes. Such difference in release profiles was attributed to a complex interplay among structure, hydrophobicity, and degradability of polyurethanes, the size and hydrophobicity of drugs, and drug-polymer interactions. Different drug-polyurethane combinations modulated the distribution and location of the drugs in polymer matrix, thus inducing different drug release mechanisms. Our results highlight an important role of segmental structure of the polyurethane as an engineering tool to control drug release.

Phenylboronic Acid-Installed Polycarbonates for the pH-Dependent Release of Diol-Containing Molecules.

Environmental responsiveness is an appealing trait of emerging polymeric materials, as shown for a variety of pH-responsive drug delivery systems. The chemical versatility of the conjugation site and conjugate lability to physiologically relevant changes in pH will largely determine their applicability. Herein, we report on the use of a drug-polymer complex based on boronic acid-functionalized polycarbonates (PPBC) as the substrate for the pH-sensitive delivery of a diol-containing drug, capecitabine (CAPE). Complexation of CAPE with a PEGylated-PPBC block copolymer, via boronic ester formation, resulted in amphiphiles capable of self-assembling into spherical nanoparticles. We examined nanoparticle stability and release kinetics in neutral and acidic media and relate differences in release profiles and particle stability with changes to polymer chemistry. Comparison of complexed nanoparticles with their noncomplex analogues revealed striking differences in release rate and particle stability. Illustrated herein for capecitabine, the pH-sensitive dissociation of boronate esters from PPBCs can be applied in a general manner to diol- or catechol-containing solutes, demonstrating the utility of these polymers for biomedical applications.

Coprecipitation of DNA-lipid complexes with apatite and comparison with superficial adsorption for gene transfer applications

Apatite can mediate gene transfer into cells by serving as a safe and biocompatible immobilization matrix for DNA and transfection reagents. Recently, an apatite layer that immobilized DNA-lipid complexes was prepared by a coprecipitation process in a supersaturated calcium phosphate solution. This composite layer (DNA-lipid-apatite layer) showed a higher gene transfer capability than an apatite layer with superficially adsorbed DNA-lipid complexes (DNA-lipid-adsorbed apatite layer). In this study, the DNA-lipid-apatite layer and the DNA-lipid-adsorbed apatite layer were compared for their physicochemical properties and gene transfer capabilities. The higher gene transfer capability of the DNA-lipid-apatite layer compared with that of the DNA-lipid-adsorbed apatite layer was reconfirmed by a luciferase assay using epithelial-like CHO-K1 cells. Physicochemical structure analyses showed that the DNA-lipid-apatite layer possessed a larger capacity for DNA-lipid complexes than the DNA-lipid-adsorbed apatite layer. The DNA-lipid-apatite layer released DNA-lipid complexes in a slow and sustained manner, whereas the DNA-lipid-adsorbed apatite layer released them in short bursts. Consequently, the release of DNA-lipid complexes from the DNA-lipid-apatite layer was larger in amount and longer in duration than release from the DNA-lipid-adsorbed apatite layer. This difference in release profiles may be responsible for the higher gene transfer capability of the DNA-lipid-apatite layer compared with that of the DNA-lipid-adsorbed apatite layer. The coprecipitation process and the resulting DNA-lipid-apatite layer have many applications in tissue engineering.

Application of time-resolved fluorescence for direct and continuous probing of release from polymeric delivery vehicles

Though accurately evaluating the kinetics of release is critical for validating newly designed therapeutic carriers for in vivo applications, few methods yet exist for release measurement in real time and without the need for any sample preparation. Many of the current approaches (e.g. chromatographic methods, absorption spectroscopy, or NMR spectroscopy) rely on isolation of the released material from the loaded vehicles, which require additional sample purification and can lead to loss of accuracy when probing fast kinetics of release. In this study we describe the use of time-resolved fluorescence for in situ monitoring of small molecule release kinetics from biodegradable polymeric drug delivery systems. This method relies on the observation that fluorescent reporters being released from polymeric drug delivery systems possess distinct excited-state lifetime components, reflecting their different environments in the particle suspensions, i.e., confined in the polymer matrices or free in the aqueous environment. These distinct lifetimes enable real-time quantitative mapping of the relative concentrations of dye in each population to obtain precise and accurate temporal information on the release profile of particular carrier/payload combinations. We found that fluorescence lifetime better distinguishes subtle differences in release profiles (e.g. differences associated with dye loading) than conventional steady-state fluorescence measurements, which represent the averaged dye behavior over the entire scan. Given the method's applicability to both hydrophobic and hydrophilic cargo, it could be employed to model the release of any drug-carrier combination.

Formulation and Evaluation of a Pulsatile Delivery System of Losartan Potassium by Factorial Design


 The present study was aimed to prepare a time-dependent pulsed release system for the programmed release of losartan potassium for the treatment of hypertension. The core tablets of losartan potassium were prepared using wet granulation containing a superdisintegrant. The design was based on 32 full factorial design containing 2 factors evaluated at 3 levels and the experimental trials were performed on coating of the core tablets. Eudragit S100 and Eudragit L100 were used as pH dependent polymers for coating of the tablets. Factors influenced the lag time and In-vitro drug release of formulations, called as dependent factors. Dissolution studies of coated tablets in media with pH (1.2 and 6.8) showed that drug release could be modulated by optimizing the concentration of Eudragit L100: Eudragit S100. Polynomial mathematical model generated for various response variable using multiple linear regression analysis, were found to be statistically significant. Contour plots and response surface plots were drawn and optimum formulation were selected by feasibility and desirability function. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The results of in vitro dissolution studies indicated that formulation P5 is the most successful formulation of the study and exhibited lag time 5.5 h and drug release 95.23 % in 12 h. The total release pattern was very close to the theoretical release profile of pulsed release system. The study showed that lag time prior to drug release was highly affected by the coating level. The dissolution data revealed that the level of coating and the ratio of polymers are very important to achieve an optimum formulation. Stability study of the optimized formulation indicates no significant difference in release profile after a period of one month.

Release profile and characteristics of electrosprayed particles for oral delivery of a practically insoluble drug

Poly(lactic-co-glycolic acid) (PLGA) microspheres containing celecoxib were prepared via electrospraying, and the influence of three processing parameters namely flow rate, solute concentration and drug loading, on the physico-chemical properties of the particles and the drug-release profile was studied. Microspheres with diameters between 2 and 8 μm were produced and a near-monodisperse size distribution was achieved (polydispersivity indices of 6-12%). Further, the inner structure of the particles showed that the internal porosity of the particles increased with increasing solvent concentration. X-ray powder diffraction (XRPD) analysis indicated that the drug was amorphous and remained stable after eight months of storage. Drug release was studied in USP 2 (United States Pharmacopeia Dissolution Apparatus 2) dissolution chambers, and differences in release profiles were observed depending on the parametric values. Changes in release rate were found to be directly related to the influence of the studied parameters on particle size and porosity. The results indicate that electrospraying is an attractive technique for producing drug-loaded microspheres that can be tailored towards an intended drug-delivery application. Compared with the more conventional spray-drying process, it provides better control of particle characteristics and less aggregation during particle formation. In particular, this study demonstrated its suitability for preparing capsules in which the drug is molecularly dispersed and released in a sustained manner to facilitate improved bioavailability.

Development of Discriminative Dissolution Media for Marketed Gliclazide Modified-Release Tablets

In vitro release studies were performed for three commercial, modified-release brands of the anti-diabetic drug gliclazide at 30-mg strength. Dissolution media such as 0.1 N HCl (pH 1.2), acetate buffer (pH 4.5), distilled water (pH 7.0), and phosphate buffer (pH 7.4) were evaluated to develop a dissolution method for better evaluation of gliclazide formulations, as there was no official method for gliclazide modified-release tablets. Drug release followed zero-order kinetics in all dissolution media except acetate buffer, where it followed first-order kinetics. The statistically treated data show a significant difference in release rates among the brands. The similarity factor and difference factor values also show the adjustment of differences in release profiles. The drug release studies carried out in 0.1 N HCl show that this medium is the most suitable for providing sink conditions and discriminating conditions.

Effect of hydrophobic and hydrophilic additives on sol–gel transition and release behavior of timolol maleate from polycaprolactone-based hydrogel

The objective of this work was to delineate the effect of hydrophilic and hydrophobic polymeric additives on sol-gel transition and release profile of timolol maleate (TM) from poly (ethylene glycol)-poly (ε-caprolactone)- poly (ethylene glycol) (PEG-PCL-PEG)-based thermosensitive hydrogel. Polycaprolactone (hydrophobic additive) and polyvinyl alcohol (PVA) (hydrophilic additive) reduced critical gel concentration of PEG-PCL-PEG triblock polymer. The effect of PCL on sol-gel transition was more pronounced than PVA. However, with PCL no statistically significant difference in release profile was observed. The effect of PVA on release profile was more pronounced, which reduced the cumulative percentage release of TM from 86.4±0.8% to 73.7±1.8% over 316 h. Moreover, cytotoxicity of the hydrogel was also investigated utilizing rabbit primary corneal epithelial culture cells. No significant cytotoxicity of hydrogel alone or in presence of additives was observed. So, polymeric additive strategy serves as a valuable tool for optimizing TM release kinetics from PEG-PCL-PEG hydrogel matrix.