Continuous, one-step synthesis of pharmaceutical cocrystals via hot melt extrusion from neat to matrix-assisted processing - State of the art.

Use of hot melt extrusion (HME) as continuous manufacturing process in the cocrystal synthesis is of increasing interest from both industrial and academic perspective and it is seen as a newly developing branch of mechanochemistry with possible broad application in single step synthesis and formulation of pharmaceutical cocrystals. Furthermore, one-step formulation of pharmaceutical products results in combined processing of pharmaceutical cocrystal mixtures with polymers using HME, which may result in phase change or formation of amorphous solid dispersions during the material processing. The manuscript aims at providing selection guidelines and understanding of processing parameters and instrumental setup of importance to design the HME process for cocrystal synthesis.

The role of the polymer matrix in solvent-free hot melt extrusion continuous process for mechanochemical synthesis of pharmaceutical cocrystal.

Solid-state synthesis of pharmaceutical cocrystals is of contemporary interest as it offers an efficient way to modify the physicochemical properties of Active Pharmaceutical Ingredient (API) including its melting point, solubility, compressibility or physical stability, without compromising its structural integrity and bioactivity. Therefore, research of novel and emerging techniques for solvent-free, continuous and scalable methods for cocrystal formation is of paramount importance for further industrial development. In this work we form a basis for knowledge-based synthesis and formulation of model pharmaceutical cocrystal (flufenamic acid, FFA: nicotinamide, NA; 1:1) via matrix-assisted cocrystallisation (MAC) using Hot Melt Extrusion (HME).

FORMULATION AND EVALUATION OF MICROSPHERES CONTAINING LOSARTAN POTASSIUM BY SPRAY-DRYING TECHNIQUE.

Despite numerous applications of microspheres, few works devoted to the preparation of microspheres containing cardiac medications have been published. This study presents the potential of receiving microspheres containing losartan potassium, based on a matrix containing Eudragit L30D55. The study focuses on the possibilities of controlled release of losartan potassium from microspheres in order to reduce the dosage frequency, and also provides information on the effect of the addition of excipients to the quality of the microspheres.

Thermal stability and decompositions kinetics under non-isothermal conditions of imatinib mesylate α form.

The thermal decomposition and kinetic parameters of synthetized imatinib mesylate α form α form were determined by thermogravimetry (TGA/DTG) under non-isothermal conditions. The experiments were performed at a 25-940°C temperature range at five different heating rates: 2.5Kmin(-1), 5Kmin(-1), 10Kmin(-1), 15Kmin(-1) and 20Kmin(-1) per minute in a nitrogen atmosphere.

Physicochemical characterization and dissolution studies of acyclovir solid dispersions with Pluronic F127 prepared by the kneading method.

The dissolution rate of anhydrous acyclovir was improved by the preparation of physical mixtures and solid dispersions with the non-ionic polymer Pluronic F127 using the kneading method at different drug-to-polymer ratios. The obtained physical mixtures and solid dispersions were examined in terms of drug content and possible physical and chemical interactions between the drug and polymer using FTIR spectral studies, differential scanning calorimetry and powder X-ray diffraction analysis. The dissolution rate of acyclovir was determined using the rotating disk method.

THERMOSENSITIVE MICROGELS OF POLY-N-ISOPROPYLACRYLAMIDE FOR DRUG CARRIERS--PRACTICAL APPROACH TO SYNTHESIS.

The aim of the work is to present the main actual information on the preparation of polymers, derivatives of N-isopropylacrylamide, formed into microgels. The most often used comonomers, crosslinkers, and initiator systems are gathered herein. The known methods of emulsion polymerization and precipitation polymerization are also described, including the application of the surfactants, as well as the surfactant free emul- sion polymerization.

The Conductivity and pH Values of Dispersions of Nanospheres for Targeted Drug Delivery in the Course of Forced Equilibrium Dialysis.

Background: In the available literature, the problem of pH and conductivity in FED is evaluated separately, and limited mainly to the final purity of the synthesized polymer. In this study data from conductivity and pH measurements were evaluated in the context of the structure of the macromolecule.

Objectives: The aim of the study was to evaluate the conductivity and pH of dispersions of nanospheres synthesized with the use of N-isopropyl acrylamide (NIPA) as the main monomer, N,N'-methylenebisacrylamide (MBA) as the cross-linker and acrylic acid (AcA) as the anionic comonomer during the purification of dispersions via forced equilibrium dialysis (FED).

Synthesis and antibacterial properties of pyrimidine derivatives.

In this study, a series of syntheses was conducted on the pyrimidine system, obtaining bisulfite carboxyl derivatives 4 and hydroxy derivatives 5. In addition, a series of syntheses were carried out as a result of which both alkyl and aromatic amines were obtained. Then, the attempt was made to cyclize these amines in the Mannich reaction to pyrimido[4,5-d]pyrimidines 11, 12.

The impact of selected preparations of trace elements - magnesium, potassium, calcium, and zinc on the release of diclofenac sodium from enteric coated tablets and from sustained release capsules.

Background: In an aging society, many patients require long-term treatment. This fact is associated clearly with the simultaneous occurrence of lifestyle diseases such as hypertension, diabetes, and even osteoarthritis. Concomitant medications, which are a common practice, pose a major threat of an interaction between these drugs.

Stability evaluation of thermosensitive drug carrier systems based on Pluronic F-127 polymer.

The aim of this study was to evaluate the stability of thermosensitive systems based on Pluronic F-127 polymer, in aspects of their possible application in novel drug technology. A formulation was prepared without any active ingredient, consisting of 16% (w/w) of polymer dissolved in aqueous medium. Such preparation was autoclaved and then subjected to 3-month conditioning at elevated (40 degrees) and reduced (5 degrees C) temperature.

Ophthalmic drug dosage forms: characterisation and research methods.

This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient's compliance.

[Effect of the medium composition on the properties of gels based on sodium carboxymethylcellulose].

Background: Sodium carboxymethylcellulose is a hydrogel substrate used in the Drug Formulation Technology to produce skin dressings, dental gels and the ophthalmic drugs.

Objectives: To study the hydrophilic medium composition based on the sodium carboxymethylcellulose and excipients on the properties of hydrogels with 1% hydrocortisone.

Material And Methods: Sodium carboxymethylcellulose, hydrocortisone, Tween 20, Ethanol 760 g/l, propylene glycol-1,2, N,N-dimethylacetamide, aqua purificata P Ph 9th.

N-(4-Meth-oxy-phen-yl)-6-methyl-2-phenyl-5-{[4-(tri-fluoro-meth-yl)anilino]meth-yl}pyrimidin-4-amine.

The title compound, C26H23F3N4O, crystallizes with two symmetry-independent mol-ecules in the asymmetric unit, denoted A and B, which differ mainly in the rotation of the meth-oxy-phenyl ring. The -CF3 group of mol-ecule B is disordered by rotation, with the F atoms split over two sets of sites; the occupancy factor for the major component is 0.853 (4).

[Influence of the gelatin-alginate matrixes with calcium lactate in plasma coagulation system after implantation in soft tissues].

Background: Bioresorbable porous substrates from copolymers have their application in tissue engineering to culture tissues in vitro. The advantage of polymers is the production of thermoplastic elements and their ability to biodegrade in a living body. Gelatin, collagen, alginates are part of dressings used for topical administration of the drug.

[Influence of gelatin-alginian matrixes on morphological and functional changes of blood leukocytes].

Background: Knowledge of the relation of biomaterials and living tissues constitutes necessary information which should be used when composing a set of optimal carriers, e.g. for drugs or preparations supporting blood clotting.

[The effect of selected excipients on properties hydrogels on the basis Carbopol 934P].

Unlabelled: AIM OF THE STUDY. The study on the effect of absorption promotors on the properties of hydrogels prepared from Carbopol 934P basis containing 1% hydrocortisone.

Materials: hydrocortysone, Carbopol 934P, propylene glycol-1,2 N,N-dimethylacetamide purified water to P Ph 9th Ed.

5-[(3,5-Dichloro-anilino)meth-yl]-N-(3,5-dichloro-phen-yl)-6-methyl-2-phenyl-pyrimidin-4-amine.

In the title compound, C24H18Cl4N4, the pyrimidine ring makes dihedral angles of 19.1 (2), 4.1 (2) and 67.

In vivo study on the biodistribution of silica particles in the bodies of rats.

Background: Biodegradable carrier materials with nontoxic degradation products are very valuable for delivering drugs and biologically active molecules. Many organic systems (such as liposomes, micelles and polymeric nanoparticles) and inorganic systems (metal oxides and silica) have been researched for delivering active substances to organs. Silica seems to be one of the most interesting and promising materials.

Solid dispersion in pharmaceutical technology. Part II. The methods of analysis of solid dispersions and examples of their application.

In the first part of the article solid dispersions were classified the properties and methods of their preparation were described. This section presents methods of analysis of solid dispersions i.e.

Solid dispersions in pharmaceutical technology. Part I. Classification and methods to obtain solid dispersions.

There are many methods to increase solubility of a substance. These include, inter alia, preparation of solid dispersions, i.e.

The study of release of chlorhexidine from preparations with modified thermosensitive poly-N-isopropylacrylamide microspheres.

The aim of this study was to investigate and compare the release rates of chlorhexidine (CX) base entrapped in the polymeric beads of modified poly-N-isopropylacrylamides (pNIPAMs) at temperatures below and over the volume phase transition temperature (VPTT) of synthesized polymers: pNIPAM-A with terminal anionic groups resulting from potassium persulfate initiator, pNIPAM-B with cationic amidine terminal groups, and pNIPAM-C comprising anionic terminals, but with increased hydrophobicity maintained by the N-tert-butyl functional groups. The preparations, assessed in vitro below the VPTT, release an initial burst of CX at different time periods between 120 and 240 min, followed by a period of 24 h, when the rate of release remains approximately constant, approaching the zero-order kinetics; the release rates for the polymers beads are as follows: pNIPAM-C>pNIPAM-B>pNIPAM-A. The pattern of release rates at temperature over the VPTT is as follows: pNIPAM-C>pNIPAM-A>pNIPAM-B.

[Influence of hydrophiling agents on gel formation rate on Carbopol base].

The aim of the study was to assess the impact of substrate composition on the physicochemical and pharmaceutical availability of hydrocortisone. Gels prepared on the basis of contained varying amounts of Carbopol propylene glycol-1,2, and polyethylene glycol 200. Applied hydrophilic substances affect the diversity of hydrocortisone half release times from hydrogels.

[In vitro evaluation of the gels properties prepared thermosensitive polymers as vehicles for administration substance by injection].

The aim of this study was to prepare a thermoresponsive formulations, which are a carrier for substance administered directly into site of action and which obtain sol-gel transitions at physiological ranges of temperature. The investigated formulations of liquid consistency at room temperature were obtained in sterile conditions on the basis of nonionic polymers Pluronic F-127, Pluronic F-68 and anionic polymer hyaluronic acid in different concentrations. The sol-gel transition temperature of the formulations was investigated and their physicochemical properties such as pH, density, osmotic pressure, sol-gel transition temperature, texture and release of vancomycin hydrochloride were studied.

N-(2-Fluoro-phen-yl)-5-[(4-meth-oxy-phen-yl)amino-meth-yl]-6-methyl-2-phenyl-pyrimidin-4-amine.

The conformation of the title mol-ecule, C(25)H(23)FN(4)O, is mainly determined by an intra-molecular N-H⋯N hydrogen bond closing a six-membered ring and the dihedral angles between the pyrimidine ring and the three benzene rings which are 12.8 (2), 12.0 (2) and 86.