Development of an amorphous based sustained release system for apremilast a selective phosphodiesterase 4 (PDE4) inhibitor.

Apremilast is a selective PDE4 inhibitor and has been approved for several inflammatory disorders. It is classified as a BCS-IV drug and has 7 polymorphic forms. In this research we report the development of an ASD based sustained-release (SR) drug delivery system.

Oleic acid-reinforced PEGylated polymethacrylate transdermal film with enhanced antidyslipidemic activity and bioavailability of atorvastatin: A mechanistic ex-vivo/in-vivo analysis.

To enhance the poor bioavailability and extensive liver metabolism of atorvastatin calcium (ATC), we have developed an oleic acid-reinforced PEGylated polymethacrylate (OLA-PEG-E-RLPO) transdermal film as a convenient and alternative delivery system. The effect of varying levels of Eudragit RLPO, PEG 400, and oleic acid on the target product profile was optimized through Quality by Design (QbD) approach. The ATC-loaded OLA-PEG-E-RLPO transdermal films were evaluated in ex-vivo experiments using full thickness skin, utilizing Franz cell studies, and undergone in-vivo pharmacokinetics/pharmacodynamics (PK/PD) assessment, using poloxamer-induced dyslipidemic Sprague-Dawley rats.

Hot-melt extrusion based sustained release ibrutinib delivery system: An inhibitor of Bruton's Tyrosine Kinase (BTK).

Ibrutinib (IB) is the first Bruton s tyrosine kinase (BTK) inhibitor classified as BCS class-II, with multiple polymorphic forms. Development of its amorphous solid dispersion (ASD) is an effective approach to overcome drug's poor solubility and concerns regarding metastable polymorphic forms. In this work, Hot Melt Extrusion (HME) was used to develop robust ASD of ibrutinib and copovidone at different ratios.

Release rate determination from in situ gel forming PLGA implant: a novel 'shape-controlled basket in tube' method.

Objectives: This study aimed to examine the impact of syringe-needle assembly differences in making implants of different shapes as well as its influence on the release kinetics and investigate the release kinetics of the in situ forming implant under various release arrangements.

Methods: PLGA in situ forming implant was prepared in different shape and then subjected to in vitro release testing. Mathematical modelling was used to investigate drug release mechanisms.

Delivery Considerations of Highly Viscous Polymeric Fluids Mimicking Concentrated Biopharmaceuticals: Assessment of Injectability via Measurement of Total Work Done "W".

An account is given of the recent development of the highly viscous complex biopharmaceuticals in relation to syringeability and injectability. The specific objective of this study is to establish a convenient method to examine problem of the injectability for the needle-syringe-formulation system when complex formulations with diverse viscosities are used. This work presents the inter-relationship between needle size, syringe volume, viscosity, and injectability of polymeric solutions having typical viscosities encountered in concentrated biologics, by applying a constant probe crosshead speed on the plunger-syringe needle assembly and continuously recording the force-distance profiles.

Amorphous-based controlled-release gliclazide matrix system.

The aim of this study was to develop a hydrophilic oral controlled release system (CRS) using the amorphous form of gliclazide, a BCS class II compound, listed on the WHO list of essential medicines. For this purpose, spray-dried dispersions (SDDs) of gliclazide were produced using various grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) or copovidone as carrier under fully automated conditions. The solid-state properties of prepared SDDs were characterized using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), modulated differential scanning calorimetry (MDSC), and Fourier transform infrared spectroscopy (FTIR).

Supersaturated controlled release matrix using amorphous dispersions of glipizide.

Spray dried dispersions (SDDs) of glipizide, a BCS Class II model drug, were prepared using various grades of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and copovidone S-630 as carriers. The SDDs appeared as a single amorphous phase with up to 60% drug loading level as revealed by X-ray powder diffraction (XRPD), modulated differential scanning calorimetry (mDSC) and scanning electron microscopy (SEM). Supersaturated micro-dissolution testing of various SDDs in fasted state simulated intestinal fluid showed prolonged supersaturation state (up to 180min) with solubility increases of 5.

Mechanistic Approach to Understanding the Influence of USP Apparatus I and II on Dissolution Kinetics of Tablets with Different Operating Release Mechanisms.

This article provides an analysis of dissolution kinetics associated with formulations subjected to different dissolution methods with the purpose of revealing credible direction on selection of apparatus type and hydrodynamics on in vitro drug release profiles using three different formulations. The dissolution kinetics of immediate release (IR) and controlled release (CR) ibuprofen tablets under different hydrodynamic conditions were determined, and potential existence of any correlation between USP apparatus I and II were analyzed using adequate kinetic models. Two types of CR tablets based on PEO (polyethylene oxide-N80) and HPMC (hydroxypropyl methylcellulose- K100M) polymers were prepared.

Solid-state interactions at the core-coat interface: physicochemical characterization of enteric-coated omeprazole pellets without a protective sub-coat.

Conventionally, scanning electron or transmission microscopy, Raman and near infrared (NIR) spectroscopy, terahertz, florescence, and nuclear magnetic resonance imaging have been used to characterize functional coating structure. This study highlights the use of fluorescence microscopy to investigate the physicochemical stability and coating integrity of the commercially available enteric-coated omeprazole pellets containing a basic excipient and prepared by extrusion and spheronization or drug layering on the nonpareil seed, immediately followed by enteric coating (i.e.

Influence of colloidal silicon dioxide on gel strength, robustness, and adhesive properties of diclofenac gel formulation for topical application.

The objective of this study is to identify the extent of stiffness, adhesiveness, and thixotropic character of a three-dimensional gel network of a 1% diclofenac sodium topical gel formulation in the presence and absence of colloidal silicon dioxide (CSD) and assess its ease of application and adhesiveness using both objective and subjective analysis. The 1% diclofenac gel was mixed with different amounts of CSD (e.g.

A novel approach in distinguishing between role of hydrodynamics and mechanical stresses similar to contraction forces of GI tract on drug release from modified release dosage forms.

The objective of this study was to determine the influence of mechanical stresses simulating gastrointestinal contraction forces of 2.0 N (stomach) and 1.2 N (intestine) on the gel properties and drug release characteristics from sustained release swelling and eroding hydrophilic matrices during dissolution studies.

Psychometrics of the scale of attitudes toward physician-pharmacist collaboration: a study with medical students.

Background: Despite the emphasis placed on interdisciplinary education and interprofessional collaboration between physicians and pharmacologists, no psychometrically sound instrument is available to measure attitudes toward collaborative relationships.

Aim: This study was designed to examine psychometrics of an instrument for measuring attitudes toward physician-pharmacist collaborative relationships for administration to students in medical and pharmacy schools and to physicians and pharmacists.

Methods: The Scale of Attitudes Toward Physician-Pharmacist Collaboration was completed by 210 students at Jefferson Medical College.

Application of a novel symmetrical shape factor to gastroretentive matrices as a measure of swelling synchronization and its impact on drug release kinetics under standard and modified dissolution conditions.

Objectives: We have assessed the kinetics of drug release in relation to the full or partial hydration and swelling of matrices under standard and modified United States Pharmacopeia (USP) apparatus II using a novel index, defined as the symmetrical shape factor. The symmetrical shape factor describes the regularity of the hydration rate of the matrix perimeter relative to its central regions.

Methods: Monolithic and three-layer matrices based on hypromellose, polyethylene oxide, Kollidon SR, theophylline, diltiazem hydrochloride and alfuzosin hydrochloride were subjected to dissolution testing.

Development and in-vitro evaluation of a colon-specific controlled release drug delivery system.

The major challenges in targeting drug to various parts of the gastrointestinal tract include control of drug release with respect to its environment and transit time. These two variables should be taken into consideration in designing a rational colonic drug delivery system. To this end, a swelling matrix core containing pectin, hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose and 5-aminosalicylic acid was developed.

Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system.

A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.

Development of a robust once-a-day glipizide matrix system.

The robustness of a new hydroxypropylmethylcellulose (HPMC) based modified release glipizide (10 mg) formulation was studied. The tablet formulations were prepared by dry blending the ingredients and direct compression, incorporating a range of release modifying agents up to +/-20% w/w relative to an optimized formulation. The dissolution was assessed in 900 mL pH 6.

Role of surfactant and pH on dissolution properties of fenofibrate and glipizide--a technical note.

The purpose of this research was to use our previously validated dynamic injection apparatus as a rapid method for screening pH-adjusted formulations of a new vancomycin analog, Van-An, for their potential to precipitate upon dilution. In 1 vial, Van-An was reconstituted according to the manufacturer’s instructions. In a separate vial, the Van-An formulation’s existing phosphate buffer species was supplemented with acetate buffer, which has a pKa in the desired range: between the pH values of the formulation (pH 3.

Development of a controlled release low dose class II drug-Glipizide.

The purpose of this study was to develop a new monolithic matrix system to completely deliver glipizide, a Biopharmaceutics Classification System (BCS) Class II drug in a zero order manner over an extended time period. Two approaches were examined using drug in formulations that contain swellable hydroxypropylmethylcellulose (HPMC) or erodible polyethylene oxide (PEO). The matrices were prepared by dry blending selected ratios of polymers and ingredients using direct compression technique.

Application of powder rheometer to determine powder flow properties and lubrication efficiency of pharmaceutical particulate systems.

The objective of this study was to understand the behavior of particulate systems under different conditions of shear dynamics before and after granulation and to investigate the efficiency of powder lubrication. Three drug powders, metronidazole, colloidal bismuth citrate, and tetracycline hydrochloride, were chosen as model drugs representing noncohesive and cohesive powder systems. Each powder was individually granulated with microcrystalline cellulose and 5%PVP as a binder.

Development of a simple analytical methodology for determination of glucosamine release from modified release matrix tablets.

A simple spectrophotometric method for determination of glucosamine release from sustained release (SR) hydrophilic matrix tablet based on reaction with ninhydrin is developed, optimized and validated. The purple color (Ruhemann purple) resulted from the reaction was stabilized and measured at 570 nm. The method optimization was essential as many procedural parameters influenced the accuracy of determination including the ninhydrin concentration, reaction time, pH, reaction temperature, purple color stability period, and glucosamine/ninhydrin ratio.

Release characterization of dimenhydrinate from an eroding and swelling matrix: selection of appropriate dissolution apparatus.

The objective of this study was to evaluate the effect of various hydrodynamic conditions on drug release from an eroding and gel forming matrix. For this purpose, dimenhydrinate was formulated with hydroxypropyl methyl cellulose and polyethylene oxide into matrix tablets and the drug release in deionized water was evaluated spectrophotometrically, using multiple dissolution methods, namely, compendial USP 27-apparatus I-III, and a modified apparatus II (paddle over mesh). Various hydrodynamic conditions were examined at the agitation rates of 50 and 100 rpm for apparatus I and II, and 5 and 8 dpm for apparatus III.

Novel modulation of drug delivery using binary zinc-alginate-pectinate polyspheres for zero-order kinetics over several days: experimental design strategy to elucidate the crosslinking mechanism.

A Box-Behnken design was applied to mathematically establish whether different degrees of crosslinking were induced by Zn2+ and Ca2+ ions in polyspheres composed of alginate and/or pectin, and the model drug ibuprofen. Based on their different crystal structures and coordination numbers, a theoretical model was proposed demonstrating that Zn2+ ions preferentially crosslink alginate and pectin. In addition, the lower coordination number of Zn2+ (4-6) would significantly retard hydration of both polymers, as opposed to Ca2+ (7-9).

A novel approach in the assessment of polymeric film formation and film adhesion on different pharmaceutical solid substrates.

The purpose of this study was to evaluate the nature of film formation on tablets with different compositions, using confocal laser scanning microscopy (CLSM), and to measure film adhesion via the application of a novel "magnet probe test." Three excipients, microcrystalline cellulose (MCC), spray-dried lactose monohydrate, and dibasic calcium phosphate dihydrate, were individually blended with 0.5% magnesium stearate, as a lubricant, and 2.

Analysis of macromolecular changes and drug release from hydrophilic matrix systems.

The influence of water-soluble and insoluble excipients on dynamics of hydration, front movement, erosion, and drug release from hydrophilic matrix tablets containing water-soluble drug was studied. Tablets were manufactured by direct compression, and their un-constrained swelling behavior and gel strength were assessed with a texture analyzer. Dissolution was performed using USP 26 apparatus II modified by insertion of a mesh to prevent sticking of tablets to the bottom of the vessel and to allow free three-dimensional matrix swelling.