Usefulness of Rosen's postulate for studying the relationship between the structure of cholic acid oxyethylation products and the process of solubilization of lipophilic therapeutic agents (BCS class II and IV) in aqueous solutions in equilibrium.

We verified the usefulness of "Rosen's postulate", i.e., the logarithm of reciprocal concentration of surfactant--log(1/cPi=20) by which the surface tension of a solution can be decreased by 20 mJ/m2 in relation to water (physiological value gamma25 = 48-52 mJ/m2) in the evaluation of the applicatory properties of cholic acid oxyethylation products. Moreover, the values of deltaG0m for solubilizers and their micellar adducts with diclofenac, naproxen, and loratadine constituted the basis for estimating the thermodynamic value of "Rebinder's effect", associated with change in the state of matter of therapeutic agent. We determined critical micellar concentration for the aqueous products of oxyethylation and for micellar adducts with diclofenac, naproxen, and loratadine, and used these values to calculate (thermodynamic potential of micelle formation).

Surface activity of novel surface active compounds, products of catalytic oxyethylation of cholic acid and their micellar adducts with selected lipophilic therapeutic agents.

The aim of this study was to determine the surface activity parameters of novel surface active compounds, products of catalytic oxyethylation of cholic acid, and their micellar adducts with selected lipophilic therapeutic agents (diclofenac, loratadine, naproxen and rutin). High solubility of lipophilic naproxen was observed in the environment of aqueous solutions of the cholic acid oxyethylation products as suggested by determined factual solubility and the value of micellar partition coefficient (K(w)(m)). Determined surface activity of surfactants described by various physicochemical characteristics (gamma(cmc)(25), cmc, deltaG(m)(o) and A(m)) suggested their compatibility with physiological values of the surface activity of plasma (48.0-52.0 mJ/m2) and lacrimal fluid (46.0-52.0 mJ/m2). Calculated values of HLB(1)(HNMR) and n(TE) of the micellar adduct in solid phase (solid dispersion) corresponded to an increase in its hydrophilicity, and, therefore, suggested possible mechanisms and site of diclofenac, loratadine, naproxen and rutin solubilization in the micellar structure (core or palisadic layer).

Solubilizing properties of new surface-active agents, products of catalytic oxyethylation of cholic acid.

Solubilizing properties of aqueous solutions of a series of surface-active agents, products of oxyethylation of cholic acid, were examined in the present study. The content of oxyethylated segments determined by means of the 1H NMR method enabled the verification of the molecular mass of surfactants along with the calculation of the structural hydrophilic-lipophilic balance (HLB), the solubility parameter delta1/2, and the required solubility level of balance HLB(R). Viscosimetric measurements enabled the calculation of the limiting viscosity number, the content-average molecular mass, the effective volume, the hydrodynamic radius of the surfactant micelle and their equilibrium adducts with rutin, diclofenac and loratadine (BCS Class II and III). By means of the spectrophotometric method (UV) the amount of the solubilized diclofenac, loratadine and rutin (rutoside) was determined in the equilibrium system (saturated solution) in the environment of aqueous solutions of cholic acid derivatives of n(TE) = 20-70. The obtained results serve as a basis for determining the solubilization mechanism of lipophilic therapeutic products and indirectly for estimating the influence of the above process on pharmaceutical as well as biological availability of a micellar adduct from model drug forms (Lindbladt lithogenolitic index).

[Surface-active agents from the group of polyoxyethylated glycerol esters of fatty acids. Part II. Chromatographic analysis and basic viscosity parameters as a estimate criterion of efficiency of catalytic oxyethylation of Lard's fractions (Adeps suillus FP VII)]. / Zwiazki powierzchniowo czynne z grupy polioksyetylenowanych estrów kwasów tluszczowych z gliceryna. Czesc II. Analiza chromatograficzna i podstawowe wielkosci lepkosciowe produktu jako kryterium oceny efektywnosci procesu katalitycznego oksyetylenowania frakcji smalcu wieprzowego (Adeps suillus FP VII).

The catalytic oxyethylation products of Lard's fractions and Tweens--as a reference products, were analised by chromatographic analysis HPLC and GPC. The above part was determination average molecular weights dispersion (Mw I Mn) and the content of polyethylene glycols (PEG), which are obtained during catalytic oxyethylation, and determination iodine value of the product (L(J2)). Viscosity measurements were carried out by Ubelohde method and enabled determination of basic viscosity and hydrodynamic parameters. The obtained results indicate that, comparing reference products--polysorbates, Tweens, products of triglycerides oxyethylation contain significantly less, in some cases very small amount of polyethylene glycols (PEG), and also maintained a high amount of unsaturated fatty acids (oleic acid), which is proven by the iodine value. Numerical value n(s) /H2O/ confirms important disparity of micells palisad structure, which are created based on oxyethylated triglycerides nTE = 40. That indicates significant solubilization possibilities of their aqueous solutions Cexp < or = Cmc.

[Surface-active agents from the group of polyoxyethylated glycerol esters of fatty acids. Part I. Basic thermodynamics values of a structure, and the level of hydrophilic/lipophilic balance (HLB) of the oxyethylenation products of Lard's fractions (Adeps suillus FP VI)]. / Zwiazki powierzchniowo czynne z grupy polioksyetylenowanych estrów kwasów tluszczowych z gliceryna. Czesc I. Podstawowe wielkosci termodynamiczne struktury a poziom równowagi hydrofilo-lipofilowej (HLB) produktów oksyetylenowania frakcji smalcu wieprzowego (Adeps suillus FP VI).

Research was conducted into the properties and identity of the oxyethylenation products of triglycerides derived from Lard (Adeps suillus) using original, stereoselective catalyst K-4. Determined of drop-point temperature -Tk (273.15 + t degrees C) allowed for calculation coefficients of volumetric dilatability--alpha (v0), linear dilatability--alpha(l0) as well as structural viscosity of the product (eta) in the state of equilibrium liquefaction. The solubility parameter delta(1/2) and the required numerical value of HLB(R )were calculated for oxyethylated product's fractions. The number of oxyethylated segments -n(TE) was determined by 1HNMR method, it made possible to estimate the weight-average molecular mass Mw, and also structural (m. Griffin) and analitycal (m. 1HNMR) level of hydrophilic/lipophilic balance--HLB. The results obtained in the course of research served as a basis for determine application properties of oxyethylated products of triglycerides fractions, in particular for the purpose of examination them for using as a transdermal passage promotors and micellar solubilizers for lipophilic therapeutic agents belonging to BCS Class II and III.

The influence of polymeric excipients on the process of pharmaceutical availability of therapeutic agents from a model drug form. Part I. In formulations with controlled disintegration and release time.

Pre-formulation research was conducted on the application of Ex. Echinaceae aq. siccum in the production of a quickly disintegrating suspension tablet, a lozenge with kariostatic sugar alcohols (mannitol, sorbitol), and, above all, a solid drug form with controlled release of therapeutic agents included in the extract. Morphological parameters of tablets obtained in the course of experiment were estimated and the profiles of the release (diffusion) ofhydrophilic therapeutic agents into model receptor fluids with varying values of osmolarity (0.1 mol HCl approximately 200 mOsm/l, hypotonic hydrating fluid approximately 143 mOsm/l, and compensatory paediatric fluid approximately 272 mOsm/l) were examined. The study focused on the technological problem of determining the effect of hydrogel Carbopol structure on the ordering of diffusion ofhydrophilic therapeutic agents from a model drug form (a tablet) into model fluids with variable osmolarity.

Chromatographic analysis of new nonionic surfactants of oxyethylation products in the presence of calcium catalyst of rapeseed oil fatty acid methyl esters (RME).

Various methods of chromatographic analysis (GPC, HPLC, TLC) were used to estimate qualitatively and quantitatively the product of oxyethylation of rapeseed oil acid methyl esters (RME). The investigation enabled to evaluate PEG content in the product. The method of eliminating insignificant quantity of PEG found in oxyethylation products of n(TE) < or = 20 was presented. The data of thin-layer chromatography obtained in the course of research constitute a point of departure for calculating n(TE) content and HLB level.

[Microcrystalline cellulose and their flow -- morphological properties modifications as an effective excpients in tablet formulation technology containing lattice established API and also dry plant extract]. / Celuloza mikrokrystaliczna i jej granulometryczno -- morfologiczne modyfikacje, jako efektywne substancje pomocnicze w technologii tabletkowania srodków leczniczych o ustalonej strukturze krystalograficznej, a takze suchych mianowanych ekstraktów roslinnych.

The production technology of powder cellulose (Arbocel) and microcrystaline cellulose (Vivapur) and their application in the composition of direct compression tablet mass was provided. The function of silicified microcrystaline cellulose type Prosolv in the direct compression process of dry plant extract was discussed. An analysis of the chemical structure of cellulose fiber (Vitacel) enabled determining its properties and applications in the manufacture of diet supplement, pharmaceutical and food products.

[Starch and its derivatives as excipients in oral and parenteral drug form technology]. / Skrobia i jej pochodne jako substancje pomocnicze w technologii doustnej i parenteralnej postaci produktu farmaceutycznego.

The morphological and structural properties of basic types of starch used as excipients in solid drug form technology with reference to its bioadhesive properties with fully polymer biodegradation. The production technology and application of: carboxymethyl starch (CMS), pregelled starch, hydroxyethyl starch (HES), hydroxypropyl starch (HPS) and the share of modified starch in technology of selected food products is provided. The authors focus on hydroxyethyl starch, which is used not only as blood and plasma substitution but also as drug camouflage agent in sports competition. In papers were presented based on literature data actually used types of starch and their chemical modifications products in drug forms and food technology.

[A chromatographic and surface-activity analysis of the fractions of Rokopols, block copolymers of propylene oxide and ethylene oxide separated from the technical product]. / Analiza chromatograficzna i aktywnosc powierzchniowa frakcji Rokopoli kopolimerów blokowych tlenku propylenu i tlenku etylenu wydzielonych z produktu technicznego.

A metod of refininig technical Rokopols, products of copolymerization of ethylene oxide and propylene oxide of 30p160, 30p27 and 30p10 type was developed. The course of the relation between R(f)(R(m)) and the number of oxyethylene segments n(TE) in the molecule of the homological series ofpolyethyleneglycols (PEG) was used to examine the content of n(TE) in the refined fractions of Rokopols. For the aqueous solutions of Rokopols weight-average molecular mass M(w) was calculated and the surface tension coefficient gamma25 was determined on the basis of the stalgmometric method. The value of the critical micellar concentration (cmc) and the thermodynamic potential for micelle formation (DeltaG(m)(0)), which facilitates the assessment of the solubilizing abilities of the investigated class of copolymers, were estimated.

Equilibrium solubilization of lipophilic therapeutic agents by aqueous solutions of products of catalytic oxyethylation of Croda-type lanolin as model excipients of the class of non-ionic surface active agents.

Research was conducted into the properties and identity of the products of Croda-type hypoallergenic lanolin, which were obtained with the use of a selective catalyst (K-4) and a standard alkaline catalyst (Na/NaOH). The 1HNMR method was employed to assess the content of oxyethylated segments and the analytic level of hydrophilic-lipophilic balance (HLB). Surface activity of products soluble in water with n(TE) > or = 40 was examined and the thermodynamic potential for micelle formation deltaGm(o) was calculated. Basic viscosity and hydrodynamic values were determined for the solubilizers and their micellar adduct with ibuprofen, ketoprofen and naproxen. In addition, the amount of solubilized therapeutic agents c/s/ was examined by means of the spectroscopic method and the micellar partition coefficient--Kw(m) was estimated. The results obtained in the course of research served as a basis for determining the solubilization mechanism and the stability of the micellar adduct for the purpose of application. This enabled the commencement of technological work on the design and manufacture of a model dosage form administered to the skin and containing the products of lanolin oxyethylation.

Viscosity of hydrogel pharmaceutical products and the rate of diffusion of ibuprofen hydrotropic binding through model phase boundary in vitro.

The aim of the carried out investigations was to establish relation between rheological parameters of market hydrogels containing ibuprofen and therapeutic agent diffusion coefficient dependent on their prescription. An attempt was made to estimate rheological parameters (structural viscosity, kinetics of volatile components loss) effect on pharmaceutical availability Q and the order of the process of mass exchange through artificial and natural phase boundary. Designed for skin anti-inflammatory hydrogels containing ibuprofen in the form of hydrotropic adduct with lysine (Ibufen, Dolofast), in the form of sodium salt (Nurofen) and in the form of molecular fragmentation of acidic form (Dolgit) were tested. The rate of volatile components loss was estimated with gravimetric method, viscosity measurements of therapeutic agents aqueous solutions were performed with Ubbelohde viscosimeter, while hydrogels rheological parameters - with cone-plate digital rheometer. The rate of ibuprofen penetration through phase boundary (Viscing dialysis membrane and pig perimastoid dermis) into dialysis fluid was determined in vitro. The kinetics of this process was monitored by measuring electric conduction Deltalambda = f(t) of model dialysis fluid. Viscometric measurements of aqueous solutions of ibuprofen lysine salt and ibuprofen sodium salt, by determining boundary viscosity gradient GLL(eta) and calculation of hydrodynamic radius Robs, enabled the applicative solution of Einstein-Smoluchowski equation (D = kT/6Pi r eta) and the estimation of structural value of therapeutic agent diffusion coefficient. Tracing the dependence between diffusion coefficient and shear rate enabled to recognize the preferences of preparations to the process of mass exchange on the phase boundary. An association was confirmed between the determined and calculated rheological parameters and the process of mass exchange on phase boundary through selected dialysis membranes. Mass exchange on phase boundary was found to be the derivative of the process of diffusion and its quantitative aspect depends on the kind of the applied membrane (it is the function of the quantity of statistically distributed pores on the unit of its surface [cm2]). Ibuprofen penetration through an artificial and natural phase boundary is complex. Its mechanism is between the kinetics of "0" and "II" order. The quantitative differentiation of the process of mass exchange between hydrotropic ibuprofen forms: ibuprofen lysine salt > ibuprofen sodium salt > ibuprofen in the form of acid molecule results from the carried out experimental study.

Solubilizing properties of new surface-active agents, products of selective oxyethylation of cholic acid. Part I.

Research was conducted into the properties and identity of the products of oxyethylation of cholic acid, which were obtained with the use of a selective catalyst (K4). The 1HNMR method was employed to assess the content of oxyethylated segments and the analytic level of hydrophilic-lipophilic balance (HLB). Surface activity of the products of oxyethylation in water and 0.1 M HCL was examined and cmc and gamma(25)cmc were determined. These were employed to calculate the thermodynamic potential for micelle formation deltaG(o)m and the surface occupied by the lipophilic structure of the surfactant at the phase boundary. Basic viscosity and hydrodynamic values were determined for the solubilizers and their micellar adducts with diclofenac, ketoprofen, fenofibrate, gemfibrozil and nifedipine. In addition, the amount of solubilized therapeutic agents c/s/ was examined by means of the spectroscopic method and the H/L balance in a solid state. The results obtained in the course of research served as a basis for determining the solubilization mechanism and the stability of the micellar adduct for the purpose of application.

Solubilizing and lithogenolitic properties of water solutions of non-ionic surfactants of cholesterol oxyethylenation products.

Research was conducted into the properties and identity of the products oxyethylenation of cholesterol, which were obtained with the use of a selective catalyst (K-4) and standard alkaline catalyst (Na/NaOH). The 1HNMR method was employed to assess the content of oxyethylated segments and the analytic level of hydrophilic--lipophilic balance (HLB). Basic viscosity and hydrodynamic values were determined for the solubilizers and their micellar adduct with ibuprofen, ketoprofen, naproxen and cholesterol. In addition, the amount of solubilized therapeutic agents and cholesterol as well as the micellar partition coefficient--K(m)w. was estimated. The results obtained in the course of research served as a basis for determining the solubilization mechanism and the stability of the micellar adduct for the purpose of application.

Micellar solubilization of selected non-steroidal therapeutic agents by new surface-active agents of the class of the products of oxyethylation of ursodeoxycholic acid.

A new class of non-ionic surface-active agents were synthesized by means of oxyethylation of ursodeoxycholic acid (UDOCh acid) with the application of modified generation of catalysts in the form of a model prodrug. Basic viscosity values ([eta], Meta, Ro, Robs., Omga) as well as the analytic level of hyrohilic-lipophilic balance HLB in the notation of Griffin, Davies and 'HNMR method were determined. In the state of equilibrium the solubilizing properties of aqueous solutions of the products of oxyetyenation of UDOCh acid x nTE were estimated with respect to non-steroidal therapeutic agents such as diclofenac, ibuprofen, ketoprofen, and naproxen. The surface activity of solubilizers of UDOCh acid > or = nTE = 30 type and the thermodynamic stability deltaGm of an adduct emerging in the state of equilibrium were determined.

Selected Rofams as a micellar solubilizers for diclofenac and naproxen in the environment of the standard vehicle for eye drops.

The process of the equilibrium solubilization of nonsteroidal anti-inflammatory drugs (NSAID), viz. diclofenac and naproxen, by Rofams, ie. the products of the oxyethylenating of the rape oil fatty acid methyl esters, in the environment of water solutions NaCl 9 g/l, H3BO3 19 g/l, KNO3 16 g/l, was tested. The solubilization activity of Rofam aqueous solutions was estimated with the use of the spectrophotometric method by means of the determination of the amount of the solubilized NSAID. The calculated apparent solubility of Rofam aqueous solutions was the basis for the estimation of the micellar partition coefficient K(w)m. The course of the ratio of the solubilized naproxen and diclofenac in the function of the solubilizer (Rofam R-13, R-15, R-17) exposure concentration was described by means of approximative equations with a high correlation coefficient.