New Biopolymer Nanoparticles Improve the Solubility of Lipophilic Megestrol Acetate.

As many substances are poorly soluble in water and thus possess decreased bioavailability, creating orally administered forms of these substances is a challenge. The objective of this study was to determine whether the solubility of megestrol acetate, a Biopharmaceutical Classification System (BCS) class II drug, can be improved by using a newly-synthesized surfactant (Rofam 70: a rapeseed methyl ester ethoxylate) and compare it with two references surfactants (Tween 80, Pluronic F68) at three different pH values. Spectrophotometry was used to compare the solubility profiles in the presence of three tested surfactants at pH 5.0, 7.4 and 9.0. Rapeseed methyl ester ethoxylate was found to improve the solubility of the BCS Class II drug and increase its bioavailability; It increased drug solubility more effectively than Pluronic F68. Its cytotoxicity results indicate its possible value as a surfactant in Medicine and Pharmacy.

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).

Surface-active agents from the group of polyoxyethylated glycerol esters of fatty acids. Part III. Surface activity and solubilizing properties of the products of oxyethylation of lard (Adeps suillus, F.P. VIII) in the equilibrium system in relation to lipophilic therapeutic agents (class II and III of BCS).

Research was conducted into the solubilization processes of diclofenac, ibuprofen, ketoprofen and naproxen in equilibrium conditions in the environment of aqueous solutions of oxyethylated lard's fractions (Adeps suillus, Polish Pharmacopoeia VIII). The determined thermodynamic (cmc, deltaGm(0)) and hydrodynamic (R0, R(obs), omega, M(eta)) parameters characterizing the micelle of the solubilizer and the adduct demonstrate that lipophilic therapeutic agents are adsorbed in a palisade structure of the micelle due to a topologically created so-called "lipophilic adsorption pocket". This shows that the hydrophilicity of the micelle and the adsorption layer decreases at the phase boundary, which is confirmed by the calculated values of coefficients A(m) and r x (a). The results obtained indicate the possibility of making use of the class of non-ionic surfactants which are not ksenobiotics for the modification of the profile of solid oral dosage forms with lipophilic therapeutic agents from the II class of Biopharmaceutics Classification System (BCS).

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.

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.

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.

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.

Equilibrium solubilization of diclofenac by aqueous solutions of the products of lanolin oxyethylenation.

Systematic research has been conducted on the products of catalytic oxyethylenation of lanolin. The level of hydrophilic-lipophilic balance HLB and the amount of oxyethylene segments nTE in homologous series of products were determined by means of the 1HNMR method. Viscosity and spectrophotometry measurements were used to determine solubilization indices n/s/, the micellar partition coefficient K(m)w, and the solubility quotient i25(r) of diclofenac in aqueous solutions of surfactants. The determination of basic viscosity values enabled identification of the solubilization site of diclofenac molecules. For the purpose of application, the relationship between the amount of oxyethylene segments nTE and K(m)w of diclofenac determined in an equilibrium system was defined.