Predicting Drug Release Rate of Implantable Matrices and Better Understanding of the Underlying Mechanisms through Experimental Design and Artificial Neural Network-Based Modelling.

There is a growing interest in implantable drug delivery systems (DDS) in pharmaceutical science. The aim of the present study is to investigate whether it is possible to customize drug release from implantable DDSs through drug-carrier interactions. Therefore, a series of chemically similar active ingredients (APIs) was mixed with different matrix-forming materials and was then compressed directly.

Quantification and modeling of nanomechanical properties of chlorpropamide α, β, and γ conformational polymorphs.

The nanomechanical properties of the α-, β-, and γ- conformational polymorphs of chlorpropamide were determined by the dynamic contact module continuous stiffness measurement at nanoindenter. The mechanical anisotropy of the α-polymorph was confirmed by indenting different faces, and its deformational behavior was assigned as ductile. Based on the nanoindentation results, the β and γ forms are moderately hard with plastic flow at contact points.

Novel Spray Dried Glycerol 2-Phosphate Cross-Linked Chitosan Microparticulate Vaginal Delivery System-Development, Characterization and Cytotoxicity Studies.

Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray drying technique using glycerol 2-phosphate as an ion cross-linker. The impact of a cross-linking ratio on microparticle characteristics was evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan microparticles were examined for the in vitro cytotoxicity in VK2/E6E7 human vaginal epithelial cells.

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients.

Nanoindentation allows quantitative determination of a material's response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision.

Effect of the surface free energy of materials on the lamination tendency of bilayer tablets.

Dosage forms with fixed dose combinations of drugs is a frequent and advantageous mode of administration, but their production involves a number of technological problems. Numerous interactions in a homogeneous vehicle may be avoided through the use of layered tablets. The mechanical properties of these dosage forms depend on numerous process parameters and material characteristics.

Roxithromycin-loaded lipid nanoparticles for follicular targeting.

Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug.

(14) N nuclear quadrupole resonance study of piroxicam: confirmation of new polymorphic form V.

A new polymorphic crystal form of piroxicam was discovered while preparing crystalline samples of piroxicam for (14) N nuclear quadrupole resonance (NQR) analysis. The new crystal form, designated as V, was prepared by evaporative recrystallization from dichloromethane. Three known polymorphic forms (I, II, and III) were also prepared.

¹⁴N nuclear quadrupole resonance study of polymorphism in famotidine.

(14)N nuclear quadrupole resonance (NQR) in two known polymorphs of famotidine was measured. At room temperature, seven quadrupolar sets of transition frequencies (ν(+), ν(-), and ν(0)) corresponding to seven different nitrogen sites in the crystal structure of each of the two polymorphs were found. This confirms the expected ability of NQR to distinguish polymorph B from its analog A.

Application of physicochemical properties and process parameters in the development of a neural network model for prediction of tablet characteristics.

The importance of in silico modeling in the pharmaceutical industry is continuously increasing. The aim of the present study was the development of a neural network model for prediction of the postcompressional properties of scored tablets based on the application of existing data sets from our previous studies. Some important process parameters and physicochemical characteristics of the powder mixtures were used as training factors to achieve the best applicability in a wide range of possible compositions.

Deformation properties of pharmaceutical excipients determined using an in-die and out-die method.

This study investigated deformation mechanisms of some commonly used pharmaceutical fillers, such as microcrystalline cellulose, lactose, dicalcium phosphate, isomalt and cornstarch, using a combination of the in-die and out-die method with the Heckel and Walker models. The tableting mixtures contained of 98.5% (w/w) filler, the rest consisted of dry binder and an antiadhesive agent.

Characterization of agglomerated carvedilol by hot-melt processes in a fluid bed and high shear granulator.

The purpose of this study was to prepare and characterize granulated carvedilol by melt-in and spray-on melt granulation in a fluid bed and a high shear granulator. Granulates having comparable particle size distribution and good flow properties were obtained with proper adjustment of process parameters for each binder (poloxamer 188, polyethylene glycol 4000, and gliceryl monosterate), procedure (spray-on and melt-in) and equipment (fluid bed and high shear granulator). In-line probes for particle size measurements proved to be a useful tool for determining the end point of melt granulation.

Addressing potent single molecule AFM study in prediction of swelling and dissolution rate in polymer matrix tablets.

Our goal was to understand and thus be able to predict the swelling behavior of xanthan matrix tablets in media of various pH and ionic strengths using data obtained from single xanthan molecules and films with atomic force microscopy. Imaging was performed in 1-butanol using contact mode AFM in order to characterize single xanthan chains prepared from various solutions. Image analysis was used to calculate the molecular contour, persistence length, and radius of gyration.

A novel fluorescent probe for more effective monitoring of nanosized drug delivery systems within the cells.

To improve visualization of nanoparticles within the cells' compartments, we synthesized a coumarin based fluorescent derivative, tetradecyl diethylamino coumarin amid, 14-DACA. In this compound the coumarin chromophore is linked with a tetradecyl alkyl chain that contributes to lipophilicity and slightly amphiphilic character of this probe. 14-DACA exhibits good biocompatibility, its solubility and emission spectrum are not sensitive to changes in pH value.

Study of Immediate Release Spherical Microparticles Containing Clarithromycin using a Hot-melt Fluid Bed Technique.

The aim of the study was to evaluate a hot-melt technique for preparation of immediate release spherical microparticles containing clarithromycin with acceptable characteristics and process yield. A modified fluid bed apparatus with rotor insert was used to prepare spherical microparticles in the size range of 125-355 µm. Poloxamer 188, PEG-32 glyceryl laurate (Gelucire 44/14) and a mixture of polyethylene glycol (PEG) 4000 with PEG 400 were used as meltable binders.

Application of 14N NQR to the study of piroxicam polymorphism.

A study was conducted to test the capability of the (14)N nuclear quadrupole resonance (NQR) method to discriminate qualitatively and quantitatively among different forms of piroxicam. Samples of commercial piroxicam form I and its monohydrate were obtained on the local market. Additionally, samples of form I and II were prepared by recrystallization in 1,2-dichloroethane and ethanol, respectively.

Nanosized particles of orlistat with enhanced in vitro dissolution rate and lipase inhibition.

Orlistat is locally acting inhibitor of gastrointestinal lipases which has been developed for the treatment of obesity. The present study was designed with the intent to formulate orlistat in a different way compared to the current practice and investigate its inhibition of gastrointestinal lipases. Orlistat is considered as a technologically problematic and unmanageable substance because of waxy nature, low melting point and low chemical stability.

Structural evolution of indomethacin particles upon milling: time-resolved quantification and localization of disordered structure studied by IGC and DSC.

The amorphization of indomethacin was induced by milling. The mass fraction of the amorphous phase in the drug milled for various time intervals was determined with differential scanning calorimetry (DSC). Because the surface fraction amorphized by milling can be much higher than the mass fraction, which can have a large impact on the powder properties, a method for quantification of surface fraction amorphized by milling using inverse gas chromatography (IGC) was developed.

The compressibility and compactibility of different types of lactose.

Objective: The purpose of this study was to investigate and quantify flow properties, compressibility, and compactibility of various pharmaceutical lactose powders found on the market today (DCL-11, DCL-21, M-200, Flowlac-100, and Tablettose 70, 80, and 100).

Methods: Flow properties were estimated by measuring flow time, angle of repose, and the Hausner ratio. Particle rearrangement was studied using Kawakita's linear model.

Vitrification from solution in restricted space: formation and stabilization of amorphous nifedipine in a nanoporous silica xerogel carrier.

Purpose: The goal was to find thermodynamic criteria that must be satisfied in order to prevent formation of crystalline state of drugs within a confined space (e.g., nanopores of inorganic solid).

[Investigation of the structure of macromoleculare gels II: analysis of viscosity curves].

Viscosity curves of gels from homo-and copolymers in aqueous medium reviewed in our previous paper were studied. Viscosity vs. rate of shear, and viscosity vs.

Novel hybrid silica xerogels for stabilization and controlled release of drug.

Purpose: The goal was to show that incorporation of a model drug into a porous solid matrix with small enough pores should lead to composites in which the drug would be in the amorphous rather than in the crystalline state. Due to spatial constraints, the amorphous state was expected to be temporally highly stable.

Methods: As a porous solid matrix silica was selected, while nifedipine served as a model drug.

Surface analysis of powder binary mixtures with ATR FTIR spectroscopy.

Attenuated Total Reflectance Fourier Transform Infra Red spectroscopy (ATR FTIR) has been used for surface analysis of powder mixtures. The appearance of one component on the surface of the mixture in greater amounts than that expected from the mass or volume ratio was quantified. Coloured mixtures containing methyl orange were analysed.

Analysis of surface properties of cellulose ethers and drug release from their matrix tablets.

Detailed knowledge based on new developments, especially in analytical techniques, is needed for characterizing polymer excipients. Inverse gas chromatography (IGC) is a useful method for investigating polymer surfaces in terms of thermodynamic parameters. The aim of our work was to study the correlation between polymer surface properties determined with IGC and the mechanisms of release of water-soluble pentoxifylline and vancomycin hydrochloride from cellulose ether matrices.

[Investigation of structure of macromoleculare gels, I. Analysis of flow curves].

Six polymers with different structure were investigated. The polymers studied were as follows: methylcellulose, hydroxyethylcellulose, carboxymethylcellulose sodium, polyacrylate sodium-polyacrylamid copolymer (Hostacerin PN 73), poly(vinylpyrrolidone)-poly(vinylacetate) copolymer (Kollidon VA 64) and poly(ethylenoxide)-poly(propylenoxide) blockpolymer. Physical networks from polymers in aqueous media were prepared.

Silica coatings on clarithromycin.

Pre-crystallized clarithromycin (6-O-methylerythromycin A) particles were coated with silica from the tetraethyl orthosilicate (TEOS)-ethanol-aqueous ammonia system. The coatings had a typical thickness of 100-150 nm and presented about 15 wt.% of the silica-drug composite material.