An evaluation of the physicochemical parameters and the content of the active ingredients in original formulas containing retinol.

INTRODUCTION: Three original cosmetic formulations containing retinol as an active component with liquid crystal, lamellar, and lipid bases were prepared. The formulas contain different concentrations of retinol, that is, 0.5%, 0.3%, and 0.15%. OBJECTIVES: The aim of the study was to evaluate a spectrophotometric method for assessing the quantity of retinol in the nine cosmetic products and to determine the viscosity of each formula. MATERIALS AND METHODS: The formulations were tested for stability; final product testing was preceded by sample weighing and pH measurement as well as exposure to the light source from xenon lamp that maps solar radiation in the range of 310-800 nm. Microbiological purity test was performed according to the PN-EN ISO 29621:2011 method and viscosity carried out using a cone-plate digital rheometer (DV-III Brookfield, version 3.0) on 0.5 cm3 emulsion samples at 32°C. The retinol content in preparations was assayed by UV spectrophotometry. RESULTS: Each of prepared cosmetic products with retinol storing in a room temperature occurred to be stable. The liquid crystal emulsion has the higher viscosity than lamellar and lipid emulsions. Although the retinol concentration in lipid serum was determined with high accuracy, the method has some limitations associated with differences between the lipid cosmetic base and the lamellar and liquid crystal sera. Nevertheless, the UV spectrophotometric method described herein is a simple and highly accurate approach for determining the retinol content in lipid cosmetics: Its coefficient of correlation was R2  = 0.9982 with a relative standard deviation (n = 3) in the range of 0.5%-1.5%. CONCLUSION: The presented UV spectrophotometric method represents an effective tool for fast and accurate determination of retinol content in lipid formulations. Probably, the method could be used in studies of other retinol-based preparations, for example, medications, and for determining the effective life of retinol-containing products in storage.

Diclofenac in the treatment of pain in patients with rheumatic diseases.

Diclofenac, a phenylacetic acid derivative, is a drug demonstrating high efficacy after oral administration in the treatment of pain and physical disability in rheumatic diseases. In view of the adverse effects associated with using diclofenac, it is necessary to consider all known drug safety information before the drug is selected for therapy and the dosage regimen is set for individual patients. Selecting an oral dosage form with specific properties determined by excipients is a method to improve the availability of the drug substance and, at the same time, minimize adverse drug reactions. An alternative to tablet or capsule dosage forms is diclofenac application to the skin. The proven efficacy of this method is further improved through the use of transdermal penetration enhancers and vehicle ingredients which provide dosage forms with specific physical properties.

Influence of plasma on the physical properties of ointments with quercetin.

Effects of two independent variables - the content of quercetin (0 or 1 or 1.5 or 5 %) and the content of plasma (0 or 2 or 4 or 6 %) - on the organoleptic properties and rheological parameters of model formulations prepared on an amphiphilic base were estimated. The consistency of all ointments was uniform, and the content of quercetin and plasma lay within the predefined range. Tested ointments are non-Newtonian systems. The content of quercetin and plasma was found to have a significant effect on the rheological properties of the ointments. An increase in the content of plasma in ointments was accompanied by a significant increase in their hardness, viscosity and shear stress and a reduction of their spreadability. The best rheological properties were shown by formulation F-3, containing 1.5 % of quercetin and 2 % of plasma.

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).

[Technological and pharmacotherapeutic properties of selected drugs with modified release of diclofenac sodium]. / Wlasciwosci technologiczne i farmakoterapeutyczne wybranych produktów leczniczych o modyfikowanym uwalnianiu soli sodowej diklofenaku.

AIM OF THE STUDY: Diclofenac and its sodium salt is one of the best-known and popular therapeutic agents from the group of NSAIDs used in medicine in many various pharmaceutical forms. Therapeutic products containing diclofenac sodium salt in doses of 100 mg and 75 mg with a qualitatively and quantitatively diversified share of excipients and a variable dosage form of the drug (solid capsules, tablets with modified release) were subjected to technological and pharmaceutical analysis. The effect of solid formulation components of polymer character making the core and the coating of the pharmaceutical form of therapeutic products on the disintegration time and pharmaceutical availability in pharmacopoeial receptor fluids was estimated. MATERIALS AND METHODS: Market therapeutic products with diclofenac sodium in doses of 75 mg and 100 mg, technological analysis of the drug dosage form was conducted, disintegration time of solid oral dosage forms of the drug with diclofenac sodium salt was examined and research on pharmaceutical availability of diclofenac sodium salt from tested therapeutic products was conducted using the acid phase and the buffer phase according to the FP standards for delayed release enteral dosage forms. The experimental data was supplemented with the statistical analysis. RESULTS: There are three formulations in the form of solid capsules and one formulation in the form of a coated tablet. All therapeutic products bear features of a dosage form of modified release of diclofenac sodium salt, frequently of a delayed release formula in the duodenum or the small intestine with regard to the limitation of typical undesirable effects after taking NSAIDs. Considerable diversity between solid capsules and the tablet with modified release during disintegration or hydration and swelling has been observed. In the environment of a receptor fluid--purified water (pH = 7) the capsule Dicloberl retard disintegrates at the fastest rate in 5,49 minutes, and then in the order: DicloDuo 75 mg--8,13 minutes and Olfen 100 SR--11,27 minutes. The hydration degree of gelatin walls of capsules depends on the pH of the receptor fluid. The availability of diclofenac sodium salt in given receptor fluids confirms the fact of significant connection of clinical effectiveness of the tested pharmaceutical forms with the activity of hydrogen ions (pH) of the environment in which there are therapeutic products, and excipients used for making the pharmaceutical phase. CONCLUSIONS: Tested therapeutic products with diclofenac sodium salt are differentiated by the type of a dosage form. Dicloberl retard contains the minimally indispensable number of simple, commonly used excipients. The research on the disintegration time may only be related to the products Dicloberl retard, Olfen 100 SR and DicloDuo 75 mg treating it as the time of deformation and disintegration of a capsule. In all three types of receptor fluids, the capsule Dicloberl retard has the fastest disintegration rate. The "acid phase" demonstrated stability of the products with a slight dissolution of diclofenac sodium salt on the level 1,3-4,18% of the Q release coefficient. In the environment of artificial intestinal juice, Dicloberl retard is more effective releasing larger amounts of diclofenac sodium salt during 4 hours of exposition (differences from 10% to 14% of the Q release coefficient).

[The use of natural and synthetic hydrophilic polymers in the formulation of metformin hydrochloride tablets with different profile release]. / Zastosowanie hydrofilowych syntetycznych i naturalnych polimerów w formulacjach tabletek z chlorowodorkiem metforminy o róznym profilu uwalniania.

AIM OF STUDY: Metformin hydrochloride after buformin and phenformin belongs to the group of biguanid derivatives used as oral anti-diabetic drugs. The object of the study is the technological analysis and the potential effect of biodegradable macromolecular polymers on the technological and therapeutic parameters of oral anti-diabetic medicinal products with metformin hydrochloride: Siofor, Formetic, Glucophage, Metformax in doses of 500mg and 1000mg and Glucophage XR in a dose of 500 mg of modified release. MATERIALS AND METHODS: Market therapeutic products containing 500 and 1000 mg of metformin hydrochloride in a normal formulation and 500 mg of metformin hydrochloride in a formulation of modified release were analyzed. Following research methods were used: technological analysis of tablets, study of disintegration time of tablets, evaluation of pharmaceutical availability of metformin hydrochloride from tested therapeutic products, mathematical and kinetic analysis of release profiles of metformin hydrochloride, statistical analysis of mean differences of release coefficients. RESULTS: The percentage of excipients in the XR formulation is higher and constitutes 50.5% of a tablet mass. However, in standard formulations the percentage is lower, between 5.5% and 12.76%. On the basis of the results of disintegration time studies, the analysed therapeutic products can be divided into two groups, regardless the dose. The first one are preparations with faster (not fast!) disintegration: Glucophage i Metformax. The second group are preparations with slower disintegration, more balanced in the aspect of a high dose of the biologically active substance: Formetic and Siofor. Products with a lower content of excipients (Metformax, Glucophage) disintegrate in a faster way. The disintegration rate of the products with a higher content of excipients (Formetic, Siofor) is slower. The appearance of metformin hydrochloride concentration in the gastrointestinal contents, balanced in time, caused by a slower disintegration-dissolving of a tablet, is conducive to the reduction of gastrointestinal side effects and better tolerance of the therapeutic product by a patient. The study on pharmaceutical availability indicated relevant kinetic differences between tested therapeutic products. They are particularly visible between standard formulations and the one with prolonged release (Glucophage XR500). Its release profile bears features of kinetics similar to zero-order reactions. CONCLUSIONS: Tested therapeutic products contain a large amount of the biologically active substance in relation to the content of excipients. A higher content of excipients in a single tablet mass distinguishes Siofor in comparison with Glucophage i Metformax. The excipients used in the formulations of tested preparations are comparable. A higher percentage of binding agents (HPMC, PVP) is observed, but there is a lack of typical disintegrants which results in a longer disintegration time up to 15 minutes. Siofor disintegrates at the same time as Formetic, but longer than Glucophage i Metformax. Considering the large content of the active substance and pharmacological properties of metformin hydrochloride, such a disintegration might have beneficial consequences, because the amount of the free active substance in the gastrointestinal tract will increase over the longer time period what will reduce the level of gastrointestinal side effects. The release profiles of metformin hydrochloride from tested therapeutic products are comparable. The Glucophage XR 500 formulation with the release kinetics of metformin hydrochloride similar to the zero-order kinetics is completely different from the others. The above is confirmed by the mathematical analysis of release profiles of metformin hydrochloride from tested preparations where equations of lines describing the release profile are characterized by similar values of correlation coefficients.

[Ibuprofen release preferences of medicinal products, the market share of excipients vement of a polymer]. / Preferencje uwalniania ibuprofenu z rynkowych produktów leczniczych determinowanych udzialem substancji pomocniczych o charakterze polimerów.

On pharmaceutical market, beside technological variability of the forms of a drug with ibuprofen, there also occurs variability of chemical and crystallographic forms of ibuprofen itself. The above allows to use ibuprofen not only in the form of pure acid, but also forms of ibuprofen sodium salts or hydrophilic solubilized complexes of very good solubility in water. The above influences changeability of technological parameters measured with the use of methods of quality control being the pharmacopeal standard. On the basis of information collected in pharmacies, it can be also considered that pharmacological effect of identical forms of drugs with ibuprofen in the same dose is differently perceived by patients expecting comfort of the process of treatment, the result of which is to be effective. The above arguments induce undertaking studies on the estimation of differences occurring between particular market versions of the forms of a drug with ibuprofen.

[The application of Harpagophytum procumbens extract in anti-inflammatory preparations applied on skin produced on acrylic acid polymers base]. / Zastosowanie wyciagu z czarciego pazura w przeciwzapalnych preparatach aplikowanych na skóre, wytworzonych na bazie polimerów kwasu akrylowego.

An attempt was made to use dry standardized extract from Harpagophytum procumbens of confirmed anti-inflammatory activity in formulations applied on skin. To obtain synergy in the area of analgesic and anti-inflammatory activity formulations were produced containing plant extract and nonsteroidal anti-inflammatory drug (ketoprofen). All the preparations were prepared on the base of acrylic acid polymers (Carbopol Ultrez 10, Carbopol 980). The formulations were subjected to complementary physicochemical investigations. Viscosity parameters (structural viscosity, yield stress, thixotrophy) were determined with cone-plate digital rheometer. Potentiometric method was used to measure pH of the produced hydrogels. The test for ketoprofen pharmaceutical availability through a semipermeable membrane to acceptor fluid was performed in vitro. The rate of the process of release was tested by determining the quantity of the therapeutic agent diffusing into acceptor fluid at defined time intervals by spectrophotometric method. The effect of Harpagophytum procumbens extract components on ketoprofen diffusion was estimated. Viscosity tests revealed that all the formulations are viscoelastic systems having yield stress. All model formulations were tested 24h after production and after 6-month storage. All the formulations demonstrate rheological stability and high pharmaceutical availability of ketoprofen. The suggested formulations can be an alternative for market preparations applied on skin of anti-inflammatory and analgesic activity.

[Dry plant extracts in the prescription of dental hydrogels with Carbopol 971P]. / Suche ekstrakty roslinne w recepturze hydrozeli stomatologicznych z Carbopolem 971P.

The study assumption was to work out a prescription for dental anti-inflammatory hydrogel on Carbopol 971P base. Dry plant extracts (sage, horsetail) and nonsteroidal anti-inflammatory drug (sodium ibuprofen) were introduced into the prescription of a model hydrogel. The aim of the study was to estimate pharmaceutical availability of the applied therapeutic agents and to test their effect on physicochemical properties of the produced form of a drug. The physicochemical parameters of the produced preparation were tested. Viscosity tests were performed using cone-plate digital rheometer. Extensometric method was used to test extensibility. pH measurements were performed by direct immersing the electrode connected with pH-meter into the hydrogel samples of uniform mass. Pharmaceutical availability of therapeutic agents contained in hydrogel (active components of plant extracts, sodium ibuprofen) was estimated. The rate of the process of mass exchange was tested by spectrophotometric method determining the quantity of therapeutic agents diffusing into acceptor fluid at the same time intervals. Sodium ibuprofen is better released from the hydrogel containing horsetail extract (815.5 c.u.) than from the hydrogel of parallel prescription containing sage extract (640.8 c.u.). Hydrogels containing dry extract from horsetail have greater extensibility and lower structural viscosity as well as the value of yield stress than equivalent hydrogels containing sage extract. Introduction of sodium ibuprofen into the prescription of hydrogels with plant extracts modifies rheological parameters (greater extensibility, lower viscosity of the preparation). The tests of the kinetics of therapeutic agents release demonstrated that the presence of sodium ibuprofen in the prescription of hydrogels exerts an influence on the decrease of the effectiveness of the release of active substances contained in these extracts.

[Application of thyme extract in the prescription of dental gels produced on Carbopol base]. / Zastosowanie ekstraktu z tymianku w recepturze hydrozeli stomatologicznych wytworzonych na bazie Carbopoli.

Active components of glycol extract from thyme manifest anti-inflammatory and astringent properties which may be also used in dentistry. The assumption of this study was to work out a prescription of dental anti-inflammatory hydrogel containing nonsteroidal anti-inflammatory drug and glycol extract from thyme. The aim of this study was to assess pharmaceutical availability and physico-chemical parameters of hydrogels produced on the base of various Carbopols (974P, 971P and AA1). Pharmaceutical availability of therapeutic agents contained in the hydrogel was tested. The rate of the process of mass exchange was tested with spectrophotometric method by determining the quantity of therapeutic agents diffusing into acceptor fluid at identical time intervals. Physicochemical parameters (including viscosity) of the produced preparation were estimated dependently on the vehicle variant components (acrylic acid polymers). Viscosity tests were performed with cone-plate digital rheometer. The kinetics of volatile components from the preparation was estimated by gravimetric method. pH measurements were performed by direct immersion of the electrode connected with the pH-meter in the samples of hydrogels of the same mass. The highest pharmaceutical availability of therapeutic agents was obtained in the tests of a hydrogel with Carbopol 971P. The area under sodium ibuprofen release curve from this hydrogel was estimated as 626.06 of conventional units. The content of active components of thyme extract in the last sample collected during the test of their release was 5.2729 mg/1 cm2 of the release area. Advantageous rheological parameters as regards application such as: low value of structural viscosity (11762 mPa x s at shear rate 2.4 1/s), low value of hysteresis loop (0.51 c.u.) and yield stress (6.51 N/m2) as well as natural pH for oral cavity (6.7) were also obtained for a hydrogel with Carbopol 971P.

[The evaluation of ketoprofen pharmaceutical availability in the presence of a dry extract from goldenrod (Solidago virgaurea L.) of synthetic polymer vehicles]. / Ocena dostepnosci farmaceutycznej ketoprofenu w obecnosci suchego wyciagu z nawloci (Solidago virgaurea L.) z syntetycznych podlozy polimerowych.

The aim of this study was to produce hydrogels for topical use and having strengthened anti-inflammatory, analgesic and antirheumatic activity. To obtain the above effect dry standardized plant extract was added to enrich a formulation containing therapeutic agent (ketoprofen) from the group of nonsteroidal anti-inflammatory drugs. Dry standardized extract from Solidago virgaurea L. of confirmed anti-inflammatory activity was selected for this purpose. The derivatives of acrylic acid polymers (Carbopol Ultrez and Carbopol 980) were used as the formulation vehicles. These vehicles were selected owing to their high applicative properties--transparency, resistance to changes of temperature, perfect tactile and esthetic qualities, no sensitizing agents, no toxicity and lack of influence on therapeutic properties of the therapeutic agent and compatibility in the pharmaceutical phase. The produced formulations were exposed to basic physicochemical tests--pH, viscosity parameters (structural viscosity, yield stress and thixotropy), pharmaceutical availability and durability after six months of storage. The effect of component plant extracts on the process of ketoprofen diffusion to acceptor fluid through a semipermeable membrane was also compared. The obtained results indicate that dry standardized extract from Solidago virgaurea L. does not affect significantly the process of ketoprofen release from the tested preparations. After six months of storage the preparations with ketoprofen demonstrate rheological stability and high pharmaceutical availability.

Influence of phosphorohydrazone derivatives of benzopyrones on polymerization and viscosity of fibrin.

The synthesis and antitumour and antibacterial activity of coumarin and chromone phosphorohydrazones have been reported. This study describes influence of phosphorohydrazones derivatives of coumarin and chromone on the polymerization and viscosity of fibrin. The fibrin polymerization assay was performed by the Shen and Lorand method and the clot viscosity was measured on the basis of Shen and Lorand and Marchi and coworkers methods. Among the eight compounds tested, one coumarin derivative and two chromone derivatives showed significant activity.

Carbopol 974P in the prescription of dental anti-inflammatory hydrogels.

The aim of this study was to assess applicative properties of the produced acc. to own prescription dental anti-inflammatory hydrogel with Carbopol 974P. Ketoprofen pharmaceutical availability was tested from hydrogel with Carbopol 974P and to compare - from hydrogels of similar prescription produced on the base of xanthan gum carboxymethylcellulose sodium salt. Very high pharmaceutical availability of ketoprofen was obtained from hydrogel with Carbopol 974P which is related to specific linear crosslinking of polyacrylic acid. The tests of physicochemical properties of hydrogel with Carbopol 974P demonstrated that it has high pH not creating the risk of demineralisation after its application in oral cavity. Introduction of zinc chloride into the prescription of hydrogel with Carbopol 974P improves rheological parameters of the preparation i.e. decreases structural viscosity, the value of yield stress and increases extensibility but decreases ketoprofen pharmaceutical availability by about 15%.

Viscosity of pharmacopeial multimolecular ointment vehicles and pharmaceutical availability of a model therapeutic agent.

Viscosity was tested of basic ointment vehicles such as: white petrolatum, yellow petrolatum, anhydrous lanolin and eucerin produced by different manufacturers. Ointment vehicles of definite type differ significantly in rheological parameters. In the same group of products, the experimentally determined viscosity value of some vehicles is two-fold (petrolatum, anhydrous lanolin) or even three-fold (eucerin) higher than that of others. On the basis of rheological tests, using Einstein-Smoluchowski equation (D = kT/ 6pireta), theoretical coefficient was calculated of a model therapeutic agent--salicylic acid diffusion (-log chi2(i) = 1,22) from the tested vehicles to the external compartment. The obtained results were related to the performed in vitro measurements of the rate of salicylic acid release from the above mentioned ointment vehicles to model acceptor fluid. High correlation was observed between theoretical values of diffusion coefficients calculated on the basis of viscosity measurements and tested experimentally pharmaceutical availability of salicylic acid. It was confirmed by describing this dependence with regression equations of high correlation coefficients (r > or = 0,9667). Marked disproportions between rheological parameters of the vehicles of definite type produced by individual manufacturers are the cause of differences in pharmaceutical availability of therapeutic agents contained in these vehicles.

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.

Auxiliary substances and applicative properties of model dental gels with ketoprofen and therapeutic saline.

The aim of the study was to produce a model form of a drug of anti-inflammatory activity designed for application in oral cavity. An attempt was made to choose hydrogel vehicle which would ensure not only high pharmaceutical availability of the therapeutic agent but appropriate theological properties of the drug as well. Variant prescriptions with ketoprofen were worked out which differed in the kind of the used vehicle (xan than gum, guar gum, hydroxyethylcellulose, carboxymethylcellulose sodium salt). Introduction of polyelectrolyte solution of therapeutic salts in the form of iodic-bromic-boronic saline into the composition of the preparation aimed at not only optimizing the hydrogel therapeutic activity but also at increasing ketoprofen pharmaceutical availability. The process of ketoprofen release is most effective from a model form of a drug with cellulose derivatives (CMC-Na and HEC) being the hydrogel vehiculum in the quantity ratio 1:1. It is a system demonstrating appropriate theological properties such as: low value of yield stress and structural viscosity, insignificant water loss at 37 degrees C and good extensibility.

Polyoxyethylene fatty acid esters as potential promotors of transdermal absorption for morphine hydrochloride and sulphate.

The presence of opioid receptors mu in pathologically changed skin and mucosa justifies application of preparations with morphine salts to obtain topical analgesic activity. Numerous factors associated with the vehicle and therapeutic agent physiochemical properties affect the capability and rate of penetration of a therapeutic substance in the form of a drug into dermis. Promotors of transcutaneous absorption, which weaken the integrity of epidermal corneal layer and thus, increase therapeutic substance penetration play more and more important role. In this study non-ionic macromolecular surface active compounds from Rokacets group were suggested as potential promotors of transdermal absorption for morphine sulphate and hydrochloride. The aim of the study was to work out prescription composition of ointment with morphine salts of optimal rheological and morphological parameters and high pharmaceutical availability of the therapeutic agent (morphine sulphate, hydrochloride). Three model emulsive ointment vehicles were prepared and selected promoters of transdermal absorption were introduced into them. On the basis of the formed vehicles ointments were made with morphine sulphate and hydrochloride. The obtained vehicles and ointment preparations were subjected to rheological tests. Spreadness was determined by extensometric method and viscosity with digital cone-plate rheometer. Morphological parameters of the vehicles and ointments, such as: pH and pharmacopeal density were estimated. Carrying out direct diffusion from the surface of the preparation to acceptor fluid (to water), the amount of the released therapeutic substance in time function was determined by spectrophotometric method. The performed tests demonstrated that the investigated vehicles and ointments are non-Newtonian systems, viscoelastic and highly thixotropic. The kind of morphine salt affects the spreadness and viscosity of model ointments. Preparations with morphine hydrochloride have higher spreadness than viscosity and more alkaline pH. From among the investigated non-ionic surface active compounds Rokacet R-40 appeared to be the most beneficial promotor of transdermal absorption for both pharmacopeal morphine salts. Pharmaceutical availability of morphine sulphate and hydrochloride is the highest from ointments with its content in the vehicle prescription.

Effect of rheological parameters on pharmaceutical availability of ketoprofen from hydrogel products made on Carbopol base.

Rheological parameters were tested in market hydrogel products of anti-inflammatory activity. Their prescription was worked out on Carbopol base. The rate of volatile components loss from pharmaceutical preparations was estimated with gravimetric method, while their viscosity parameters (structural viscosity, yield stress, the area of hysteresis loop) were determined with cone-plate digital rheometer. The kinetics of the therapeutic agent (ketoprofen) release through a standard Viscing membrane to external compartment was tested in hydrogels in vitro. The aim of the study was to determine the relationship between rheological parameters dependent on the prescription of the tested hydrogels and pharmaceutical availability of ketoprofen. Pharmaceutical preparations of anti-inflammatory activity made on Carbopol base are non-Newtonian liquids diluted with shear. Due to ethanol content in their prescription, after application on skin, the increase of structural viscosity and the decrease of ketoprofen pharmaceutical availability accompany the process of volatile components loss from the surface layer of the preparation. Ketoprom hydrogel, having propylene glycol in its composition, is characterized by higher values of viscosity, hysteresis pool area and yield stress than Fastum preparation. Insignificant differences between experimentally determined in vitro areas under the curves of ketoprofen release are associated with rheological parameters of the investigated hydrogels, which was anticipated on the basis of Einstein-Smoluchowski's equation. Ketoprofen penetration from the tested pharmaceutical products on Carbopol base to the external compartment is in accordance with kinetics of "0" order and is diffusion-controlled.

Application of guar gum biopolymer in the prescription of tablets with sodium ibuprofen--quality tests and pharmaceutical availability in vitro.

The increasing interest of the technology of drug form in natural biopolymers has become the reason for undertaking investigations on the possibility of guar gum application in the prescription of oral solid form of a drug. Alternative compositions and technology of the production of tablets of regulated in time sodium ibuprofen release were worked out for children. Two series of tablets were prepared with guar gum (5 and 10% content) and a series without the biopolymer. The tablet mass in each case contained keryostatic sorbitol and bioadhesive polyvinylpyrrolidone. All tablets were tested as regards the quality of production, compliance with the requirements of Polish Pharmacopoeia VI and potential therapeutic usefulness, manifestation of which is pharmaceutical availability of the therapeutic agent (sodium ibuprofen). The tests demonstrated that the produced tablets with sodium ibuprofen have proper physicochemical properties, in compliance with Polish Pharmacopoeia VI requirements. Application of biopolymer of guar gum type as adjuvant substance contributes to the improvement of the tablet hardness parameters and prevents technological problems (lining mixture of powders to tableting machine punch). The designed tablets demonstrate proper pharmaceutical availability of over 80%. Introduction of guar gum into their prescription prolonged their disintegration time and the rate of sodium ibuprofen release, which predisposes the produced form of a drug to have the function of a tablet with slowed-down release.

The effect of saccharic alcohols on rheological parameters of dental anti-inflammatory gels and on pharmaceutical availability of sodium ibuprofen.

A prescription of model dental anti-inflammatory gels has been worked out on the base of cellulose derivatives with the content of saccharic alcohols: xylitol and sorbitol. The effect of saccharic alcohol on rheological parameters (extensibility and viscosity) of the produced gels was tested. Taking into account application, the most beneficial results of rheological tests were obtained for gels containing in their prescription both xylitol and sorbitol in the quantity ratio 1:1. These gels are characterised by high extensibility, low viscosity and low value of yield stress. Theoretical diffusion coefficient of sodium ibuprofen calculated on the basis of viscosity measurements points to the highest pharmaceutical availability of therapeutic agent from model gels with xylitol and sorbitol. The above has been confirmed by in vitro studies of the sodium ibuprofen kinetics of release from gel to the dialysis fluid.