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. Microspheres are monolithic, porous or smooth microparticles ranging from 1 to 500 microns in size. For the preparation of microspheres containing losartan potassium, the spray-drying method was used. The performed study confirmed that the spray-drying technology used to obtain microspheres meets the criteria of size and morphology of the microparticles. The assessment of the kinetics of losartan potassium release from the examined microspheres demonstrated that the release profile followed the first- and/or zero-order kinetics. The use of spray-drying techniques as well as Eudragit L30D55 polymer matrix to obtain the microspheres containing losartan potassium makes it possible to obtain a product with the required particle morphology and particle size ensuring the release of the active substance up to 12 h.

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. Finally, the procedures of lab-scale production of microgel were evaluated in the paper, with special intact on the thermosensitive N-isopropylacrylamide derivatives for application in biomedical field.

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. After determination of chemical structure using physicochemical tests, also by means of crystallographic tests, all the newly obtained derivatives underwent microbiological tests on bacterial strains and fungi. The most interesting results of the microbiological tests are included later in the study.

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.

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. Rheological parameters: viscosity, consistency and sol-gel transition characteristics were studied in 1-month interval. The significance of measured changes was evaluated by proper statistical analyses. Significant changes exceeding the established criteria (+/- 10% of every initial value) were observed during the study. Furthermore, total involution of sol-gel transition phenomenon was observed in samples stored at 40 degrees C. Results indicate the lack of stability in tested formulation at both of storage conditions. However, some regularity indicates that the stability at reduced temperature could be confirmed, if only the concentration of polymer and the measurements schedule were slightly modified.

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). The dihedral angles between the pyrimidine ring and the attached phenyl, meth-oxy-phenyl and tri-fluoro-methyl-phenyl rings are 8.1 (2), 37.5 (2) and 70.7 (2)°, respectively, in mol-ecule A, and 9.3 (2), 5.3 (2) and 79.7 (2)° in mol-ecule B. An intra-molecular N-H⋯N hydrogen bond occurs in each mol-ecule. In the crystal, two crystallographically independent mol-ecules associate into a dimer via a pair of N-H⋯N hydrogen bonds, with a resulting R 2 (2)(12) ring motif and π-π stacking inter-actions [centroid-centroid distance = 3.517 (4) Å] between the pyrimidine rings. For the A mol-ecules, there are inter-molecular C-H⋯O hydrogen bonds between an aryl C atom of meth-oxy-phenyl ring and a meth-oxy O atom of an adjacent mol-ecule. A similar inter-action is lacking in the B mol-ecules.

[The effect of selected excipients on properties hydrogels on the basis Carbopol 934P]. / Wplyw wybranych substancji pomocniczych na wlasciwosci zeli na bazie Carbopolu 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., ethanol 760 g/1, Tween 20. Dynamic viscosity test: was carried out using the Rheotest 2. The values of the shear stress and viscosity were calculated from measurements. Consistency test--TPA test was performed with Exponent Stable Micro Systems texture analyzer. Examination of pharmaceutical availability of hydrocortisone: The process of hydrocortysone release from hydrophilic base was carried out according to the method based on active substance diffusion through a semi-permeable membrane. Concentration of hydrocortysone according to Polish Pharmacopoeia 9th Ed. RESULTS: Rheological studies showed that the process is nonlinear. Tested gels shows thixotropic properties. The tension decreases with the increase in the percentage of excipients. Hardness tests showed that in comparison to the reference gel, pressure force increased in the presence of 1% of the excipients in the gel, and the reduction in the presence of 15% of the excipients. Gels are characterized with greater cohesiveness than the control preparation. The release process of the drug substance proceeds in accordance with first order kinetics. Increasing concentrations of used absorption promotors influenced on increase the number of hydrocortisone released from the hydrogels prepared on the basis of 3% Carbopol 934 F gel. CONCLUSIONS: 1. Tested gels are showing thixotropic propereties and are non-Newtonian systems. 2. The hardness and cohesiveness of the gels increases with increasing concentrations of the excipients. 3. The value of the constant release rate is increases in the presence of ethanol, Tween 20, and DMA.

[Effect of the medium composition on the properties of gels based on sodium carboxymethylcellulose]. / Wplyw skladu podloza na wlasciwosci zeli wykonanych na bazie soli sodowej karboksymetylocelulozy.

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. The dynamic viscosity were determined by the method described in a previous publication [9]. The test of the consistence: the hardness and cohesiveness of the hydrogels were tested by TPA test. Hydrocortisone release experiment was performed according to PPh 9th by the paddle apparatus. The amount of drug was determined by spectrophotometry method. RESULTS: Hydrogel dressings show thixotropic properties, they are non-Newtonian fluids. The addition of increasing amounts of excipients reduces the shear stress. Compared to the control formulations, tested hydrogels are more cohesive, have a lower hardness with addition of 1% of Ethanol, Tween 20 and higher in other cases. Pharmaceutical availability of hydrocortisone follows the first order kinetics. Excipients added to the gels are speeding up the process in the presence of DMA, but are extending process with propylene glycol-1,2, Ethanol and Tween 20. CONCLUSIONS: Tested hydrogels in the presence of Ethanol, GP-1,2, DMA, Tween 20 exhibit higher shear stress than the control formulations. Hydrogels based on the Na-carboxymethylcellulose are less hard and more cohesive. The drug release follows the first order kinetics.

[Influence of the gelatin-alginate matrixes with calcium lactate in plasma coagulation system after implantation in soft tissues]. / Wplyw matryc zelatynowo-alginianowych z mleczanem wapnia na osoczowy uklad krzepniecia po implantacji w tkanki miekkie.

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. Research was undertaken to achieve a porous gelatin-alginate matrix which could be used in therapy as among others, a carrier for a drug. OBJECTIVES: Evaluation of the impact of modified gelatin-alginate matrix on activation of plasma coagulation in vivo. MATERIAL AND METHODS: Gelatin-alginate matrix cross-linked with calcium ions was implanted in the muscle tissue of a rat. The control group constituted animals not implanted with material, but they passed the operating procedure. Blood samples of plasma coagulation test and control group were collected after 1, 2, 3, 5, 7, 10, 14 days of the procedure. RESULTS: Prolongation of APTT and shortening of PT and TT with the unchanged values of fibrinogen and the count of platelet cells was observed till the 5th day on the basis of the obtained results. Prolongation of APTT with the unchanged values of the remaining parameters of the coagulation system was observed after 7, 10 and 14 days with unchanged values of PT and TT coagulation. CONCLUSIONS: The matrix gelatin-alginate with calcium ions in the biological environment undergoes biodegradation in soft tissues. This process in the initial period influences the activation of the coagulation within the intrinsic and extrinsic system. From the 5th to 14th day the activation of coagulation was observed only in the intrinsic system.

[Influence of gelatin-alginian matrixes on morphological and functional changes of blood leukocytes]. / Wplyw matryc zelatynowo-alginianowych na zmiany morfologiczne i czynnosciowe leukocytów krwi.

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. OBJECTIVES: This paper presents an assessment of the influence of contact of gelatin-alginian matrixes with blood on leukocyte reactivity: the ability of mononuclear cells (lymphocytes and monocytes) to create a radial segmentation of nuclei--RS (the morphological change), and the ability of leukocytes to phagocytosis of yeast Saccharomyces cerevisiae cells and to produce active oxygen derivatives (functional changes). MATERIAL AND METHODS: After having contact with the matrixes, the test of induced and spontaneous RS, the phagocytic test and nitroblue tetrazolium reduction test for blood leukocytes were performed. RESULTS: The obtained results showed a decrease in the ability of mononuclear cells to form RS and in the ability of granulocytes to reduce nitroblue tetrazolium--NBT, but an increase in their phagocytic activity. CONCLUSIONS: Temporary contact of gelatin-alginian matrixes with blood did not cause any morphological changes in the leukocytes. However, changes of their reactivity were observed.

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. In the presence of pNIPAM-C, the duration between the start of the release and the attained minimal inhibitory concentration (MIC) for most of the microbes, in conditions over the VPTT, increased from 60 to 90 min. The release prolongation could be ascribed to some interactions between the practically insoluble CX particle and the hydrophobic functional groups of the polymer.

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 67.5 (2)°, respectively, with phenyl and two benzene rings, and the mol-ecular conformation is stabilized by an intra-molecular N-H⋯N hydrogen bond closing a six-membered ring with an S(6) motif. In the crystal, a pair of inter-molecular N-H⋯N hydrogen bonds connect two mol-ecules, forming inversion dimers with R2(2)(12) motifs. C-H⋯π inter-actions links the dimers into a chain running along the a-axis direction. There are also π-π stacking inter-actions [centroid-centroid distance = 3.666 (4) Å] between the benzene rings of adjacent chains.

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.: thermoanalytical methods, XRPD, FTIR, microscopic methods, dissolution studies and examples of drug forms where solid dispersions were used.

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. eutectic mixtures, solid solutions, glassy solutions and suspensions. When compared to the individual constituents prior to dispersion formation solid dispersion components are better soluble in water. Therefore, solid solutions became one of the most promising ways to modify solubility, ensuring improved bioavailability and consequently therapeutic efficacy of a substance. In this part of the publication solid dispersions were classified and described in regard to their properties and preparation methods, i.e. melting method, melt evaporation and melt extrusion methods, lyophilisation technique, melt agglomeration process as well as SCF technology and electrospinning.

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 86.1 (2)°. An intra-molecular N-H⋯F inter-action also occurs. The crystal stucture is stabilized by weak C-H⋯O and C-H⋯π inter-actions. An inter-molecular N-H⋯N inter-action is also observed.

Synthesis and antibacterial properties of pyrimidine derivatives.

The paper presents the synthesis of 1,2,3,7-tetraaryl-1,2,3,4-tetrahydropyrimido[4,5-d]pyrimidines. The structures of the obtained compounds were confirmed by crystallographic and spectroscopic analyses, and their antibacterial activity was tested on 9 selected strains, comparing chemical structure changes with increased microbiological activity. It was confirmed that aromatic residues in the hydrogenated pyrimidine ring constitute a significant element influencing antibacterial activity. Electronegative radicals increase microbiological activity, but decrease solubility of the compounds. Therefore, substituents should be selected in a manner ensuring a balanced effect. The presented crystal structure of 6f includes two stereoisomers, which we decided to isolate and compare the microbiological properties in further studies.

[Influence of polymers on hydrogels with hydrocortisone properties]. / Wplyw substancji wielkoczqsteczkowych na wlasciwosci hydrozeli z hydrokortyzonem.

Studies on the effect of polymers on physicochemical properties hydrogels for topical use. Rheological parameters were tested and pharmaceutical availability of hydrocortisone from gels. Formulation of hydrogels with 1% hydrocortisone content produced on the basis of methylcellulose, carboxymethlcellulose sodium salt and Carbopol 934 P.

[Influence of hydrophiling agents on gel formation rate on Carbopol base]. / Wplyw substancji hydrofilizujacych na wlasciwosci hydrozeli sporzadzonych na bazie Carbopolu.

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.

[The effect of the composition of stomatological dressings on Carbopol 971P and methylocelullose base on pharmaceutical availability of metronidazole]. / Wplyw skladu preparatów stomatologicznych sporzadzonych na bazie polimerów--Carbopolu 971P i metylocelulozy na dostepnosc farmaceutyczna metronidazolu.

The carried out studies allowed to propose composition of stomatological dressing makes opportunity to ensure preferable physiochemicals features for dosage forms. According to results formulations contain 1.5% Carbopol 971P, 0.13% methylocelullose and various quantity of glycerol, 1,2-propylene glycol and polyethylene glycol 400 were prepared. To compare formulation consists of only polymers dispersion (Carbopol 971P and methylocelullose) was prepared. Next to produced compound triethanoloamine to pH range 5.5-6.5 and 1% metronidazole added. Kinetics test of metronidazole release was performed in vitro using Hanson's cells and semipermable membrane. The quantity of the release metronidazole was determined by spectrophotometric method. Gel consists of 98% polymers dyspersion with 2% glycerol characterized by the largest pharmaceutical availability. The addition of 2% PEG 400 resulted in the decrease of the percentage of released substance in comparison to formulation without hydrophylisers. Metronidazole releasing was more efficient for dressings with 2% glycerol as well propylene glycol. For preparations contains glycerol (2 and 5%) as well propylene glycol as adiuvants, it was found that gels prepared on Carbopol 971P and methylocelullose revealed higher pharmaceutical availability than analogical dressings prepared with only one polymer base.

[In vitro evaluation of the gels properties prepared thermosensitive polymers as vehicles for administration substance by injection]. / Ocena wlasciwosci zeli otrzymywanych na bazie termowrazliwych polimerów, jako nosników dla substancji podawanej w postaci iniekcji.

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. In vitro release experiments indicated that the optimised platform was able to prolong vancomycin hydrochloride release and their physico-chemical properties allow for application by injection form.