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Biomedical subjects

M Sznitowska

Publications and source records attributed to M Sznitowska.

At least 19 recordsLinked to original sources
PubMed2001

Studies on the effect of pH on the lipoidal route of penetration across stratum corneum.

The effect of pH on the excised skin permeability towards two model lipophilic compounds was studied in the range of pH 1.0-10.0 and 1.0-12.0, for hydrocortisone and testosterone, respectively. Suspensions of the model compounds in appropriate buffers (0.1-0.2 M) were applied to the intact skin, delipidized skin, skin pretreated with Azone or sodium lauryl sulfate solution and the percutaneous penetration was observed for 28 h. Within the studied pH range, up to pH 11.0 no change in the penetration through the skin and skin accumulation was observed for both compounds. Significant, 3-4-fold, increase of penetration of testosterone was noted only at pH 12.0, however the change was neither fast not progressing with time. None of the pretreatment procedure influenced the observed relationship between pH and skin permeability. It is concluded that the lipoidal route of penetration is not affected by solutions at pH within the range 1.0-11.0.

Anti-Inflammatory Agents↗
PubMed2001

In vitro studies on penetration of terpenes from matrix-type transdermal systems through human skin.

Polyurethane matrices containing up to 39% of the terpenes eucalyptol, L-limonene, D-limonene, dipentene or terpinolene were produced. Release of the terpenes directly to the acceptor fluid, as well as through isolated human epidermis and dermis, was studied. In the presence of dermis the penetration profiles were very similar to the release profiles, indicating that dermis does not present a barrier for penetration of terpenes. For all terpenes the penetration was slower in the presence of epidermis (K(p) was in the range 0.21-1.8x10(-3) cm/h). Release and penetration through the epidermis and dermis were fastest for dipenetene (mixture of D-limonene and L-limonene), being at least 3-4 times faster than for D-limonene and L-limonene. Large amounts of terpenes found in epidermis (approximately 1.5 mg/cm(2)) indicate that affinity of these compounds to the stratum corneum is very high.

Administration, Cutaneous↗
PubMed2001

Submicron emulsions as drug carriers. Studies on destabilization potential of various drugs.

Few drugs have been successfully formulated as submicron emulsions. The physicochemical stability of submicron emulsions on admixture of drugs is the main factor limiting a wider use of this type of vehicle for parenteral or other routes of administration. In a short-term stability studies we have investigated 35 drugs with regard to their compatibility with 20 or 5% parenteral fat emulsions. The study has shown that interaction of drugs with submicron emulsions is complex in nature. Taking into consideration the physicochemical properties of a drug e.g. lipophilicity or ionization, it is difficult to predict changes in the physical stability of the system. If destabilization occurs it is maximal at saturated concentrations and the presence of even significant amounts of the solid phase formed by undissolved drug does not influence the short-term stability of the system. Due to the increased ratio of emulgator to oil, emulsions containing 5% of oily phase are less susceptible to destabilization than 20% emulsions.

Chemical Phenomena↗
PubMed2001

Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and solid lipid nanoparticles after rectal administration in rabbits.

The bioavailability of diazepam in rabbits after rectal administration of three formulations: organic-aqueous Relsed rectal solution (containing ethanol, benzyl alcohol and propylene glycol), submicron emulsion and solid lipid nanoparticles (SLN), was studied. Submicron emulsion contained MCT oil (20% w/w), egg lecithin and poloxamer; SLN were prepared with cetyl palmitate 10% w/v and non-ionic emulsifying agent, Plantacare. All formulations contained 4 mg/ml of diazepam and the dose administrated to rabbits was 2 mg/kg. In both submicron preparations nearly the same mean size of the dispersed particles (201-206 nm) and the fraction of the free drug in aqueous phase (0.9-1.5%) was determined. Besides very moderate prolongation of drug release, the submicron emulsion as a vehicle did not alter pharmacokinetics of diazepam when compared with the solution: the mean C(max) was 48.9+/-24.0 and 49.5+/-17.0 ng/ml, and area under the curve was 134.0+/-42.3 and 186.8+/-59.8 ng h/ml, for solution and emulsion, respectively. The low relative bioavailability, 47% compared to the solution, was observed after administration of SLN. Transmission electron microscopy pictures revealed that some of diazepam is present on the surface of the SLN and this fraction was immediately absorbed, while the diffusion of the drug in the solid core was not efficient enough to allow a complete release. It may be concluded that submicron emulsion may be a good choice of an ethanol-free drug formulation, but lipid matrix, which is solid at body temperature, is not advantageous system for diazepam rectal delivery, even if delivered as a submicron dispersion.

Administration, Rectal↗
PubMed2001

Evaluation of paracetamol suppositories by a pharmacopoeial dissolution test--comments on methodology.

Ph.Eur. and BP have introduced a dissolution apparatus for suppositories. Suitability of the apparatus for quality control of paracetamol suppositories was evaluated and the effect of experimental conditions on dissolution profiles was studied. Paracetamol suppositories containing 80-500 mg of the drug, on fatty base, were obtained from four manufacturers (A, B, C, D). The diffusion cell was modified by incorporation of an in-built thermoprobe and large difference (up to 1.7 degrees C) between temperature in the water-bath and in the dissolution chamber was observed. This effect was avoided by increasing the length of tubing immersed in the thermostat at the inlet of the cell. The most reproducible results were observed for A and C suppositories, however from suppository C the total dose of paracetamol was released after 3.5-4.5 h while the release from suppository A was slow with only 40-87% of the total dose liberated during 6 h. Suppositories B did not melt at 37 degrees C and less than 5% of the drug was released. Fast release was observed after melting when the temperature was elevated to 39.5 degrees C. The results demonstrate clearly that essentially complete melting of a suppository in the dissolution chamber is required for an appropriate dissolution of paracetamol in vitro. Disintegration time, softening time, drop point and particle size of the suspended drug were measured and the relevance of these parameters for dissolution behaviour of the preparations was discussed.

Acetaminophen↗
PubMed2001

Diazepam submicron emulsions containing soya-bean oil and intended for oral or rectal delivery.

Physically stable diazepam submicron emulsions were prepared using soya-bean oil. Diazepam concentration 4 mg/ml, suitable for rectal or oral delivery, was achieved in 20% emulsions. Mixture of egg lecithin (1.2%) and poloxamer (2.0%) has been chosen as the most suitable emulsifying agent. Composition of the emulsion may be supplemented with alpha-tocopherol and parabens. However, the system was not stable when either phenylethanol or chlorhexidine gluconate was added. Taste masking agents commonly used as food additives decreased stability of the preparation and were not efficient in elimination of a bitter taste of the drug-loaded emulsions.

Administration, Oral↗
PubMed2000

Increased partitioning of pilocarpine to the oily phase of submicron emulsion does not result in improved ocular bioavailability.

Submicron emulsions containing pilocarpine as ion-pair with mono-dodecylphosphoric acid were prepared. Physical stability of these preparations was confirmed during 4 months of storage at 4 degrees C. Approximately 50% of the drug was found in the aqueous phase of emulsion separated using an ultrafiltration technique, while the rest was present in the oily phase and interphase. The miotic effect observed in rabbits after application of the ion-pair in aqueous solution or in submicron emulsion was the same; indicating that the drug distribution into the oily phase of the colloidal vehicle does not improve ocular bioavailability.

Animals↗
PubMed2000

[Percutaneous absorption of heparin: a critical review of experimental results].

Percutaneous penetration of heparin is limited by its large molecular weight, negative charge and hydrophilicity. Although some authors did not find any significant anticoagulant effect of transdermally delivered heparin but several other papers indicate that heparin penetrates the skin barrier. The actual article provides a critical review of the in vitro and in vivo studies on percutaneous absorption of heparin and heparinoids. It is concluded that there is no sufficient evidence that heparin is able to penetrate intact skin. However under clinical conditions the integrity of the skin barrier may be changed what results in promotion of heparin penetration and justifies usage of topical drug formulations like ointments and gels.

Administration, Cutaneous↗
PubMed1999

Miotic effect and irritation potential of pilocarpine prodrug incorporated into a submicron emulsion vehicle.

Pilocarpine prodrug, O,O'-dipivaloyl(1,2-ethylene) bispilocarpic acid diester, was introduced to a submicron emulsion vehicle in a dose equivalent to 0.5% pilocarpine base, and the formulation was studied in albino rabbits using miotic assay. Compared with pilocarpine HCl 0.5% solution delayed and prolonged miosis was observed after application of the prodrug emulsion. AUC(0-6 h) values for the prodrug emulsion and pilocarpine solution were 9252+/-1345 and 6845+/-1967%xmin, respectively. The prodrug was also administered twice daily for 5 days in the form of aqueous solution or submicron emulsion in order to study ocular irritation. Irritation potential of the prodrug was significantly reduced when submicron emulsion was used as a vehicle.

Animals↗
PubMed1999

Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle.

In order to obtain a novel ocular formulation with a potential for prolonging pilocarpine activity, the drug (2.0%) was incorporated into a submicron emulsion containing soya-bean oil and lecithin as emulgator. The effect of drug incorporation into the emulsion on its physical stability and on the other hand, the potential of the vehicle to reduce drug degradation at pH higher than 5.0 was studied. The pH was adjusted to 6.5 or 5.0 and the physicochemical stability of the formulations was observed. The mean diameter of oily particles in the resulting emulsions measured by a laser diffractometer was 0.6-0.7 micron and this was larger than in a drug-free emulsion where a 0.33 micron value was measured. The formulations were physically stable for 6 months at 4 degrees C, but progressing chemical degradation of pilocarpine was noted at pH 6.5. At that pH nearly 8% of pilocarpine was degraded to isopilocarpine and pilocarpic acid, both in the emulsion and in the solution. Thus, it may be concluded that pilocarpine in submicron emulsion is not protected against degradation. The presence of pilocarpine changes the physical stability of the vehicle since the formulation was easily destabilized during autoclaving or at room temperature. In the presence of higher concentration of lecithin (2.4%) or co-emulgators (poloxamer 2.0% or Tween 80 0.5%) the mean droplet size in the emulsions was the same as in a drug-free system. However the emulsions containing poloxamer were not stable during storage. Viscosity of pilocarpine emulsions can be increased by addition of methylcellulose or sodium carmellose (1.0%), but an intensive creaming occurs in these systems. Pilocarpine base is less suitable for emulsion preparation than hydrochloride salt, and emulsions prepared at pH 5.0 show the most satisfying stability.

Chemistry, Pharmaceutical↗
PubMed1998

Intracellular or intercellular localization of the polar pathway of penetration across stratum corneum.

A pharmacokinetic hypothesis of stratum corneum with two parallel pathways, lipophilic and porous hydrophilic, is not well documented yet. Still questionable is the localization of the pores, and the present experiments were designed to elucidate the contribution of extracellular lipids and intracellular keratin to the structure of this pathway. Percutaneous penetration of baclofen, a model zwitterion, was studied in vitro using human cadaver skin. Aqueous or ethanolic saturated solutions of the drug (Cs = 4.6 and 0.4 mg/mL, respectively) were applied on the skin that was pretreated with: methanol/chloroform (Me/Ch) or acetone-chloroform (Ac/Ch) (1:1) mixtures, or with these solvents followed by 0.2% solution of sodium lauryl sulfate (SLS). As controls, baclofen penetration through the intact full-thickness skin was determined, and the fluxes were 0.18 +/- 0.08 and 0.14 +/- 0.07 microg/cm2/h for aqueous and ethanolic solutions, respectively. When Me/Ch was used for 1 h, an expected increase of the penetration was observed, but the lag time, Tlag, was still nearly 20 h. When the less polar mixture, Ac/Ch, was used, no flux enhancement was observed, and with ethanol as the vehicle, decreased penetration was even noted. No effect on baclofen penetration was observed when SLS was used for 1 h after delipidization of the skin was done with either the Me/Ch or Ac/Ch mixture. The results suggest that the polar pathway may be located intercellularly and comprises aqueous regions surrounded by polar lipids, which create the walls of such microchannels.

Baclofen↗
PubMed1994

Increased proliferation of skin cells by sublethal doses of sodium lauryl sulfate.

Most quantitative in vitro approaches to determine irritancy have examined the potential of compounds to decrease biological functions or inhibit growth of cells. Irritants, however, are known to generally have the opposite effect in vivo, i.e. to stimulate cell division. This property has not been directly studied in vitro. We examined the ability of sublethal concentrations of sodium lauryl sulfate (SLS) to stimulate cultured keratinocyte and fibroblast proliferation in vitro. The growth of keratinocytes, without added growth factors, continuously exposed to SLS for 4 days was stimulated approximately 89% compared to control. Keratinocytes exposed to SLS for 1 or 18 h were stimulated 36 and 12%, respectively, over the next 4 days of growth. Subconfluent fibroblasts were also stimulated approximately 38%. Confluent fibroblasts were stimulated 40%. All stimulations were maximal between 10(-8) and 10(-5) M added SLS. Media conditioned by keratinocytes exposed to 10(-8) M SLS were able to increase the growth of naive keratinocytes by 117%. In all experiments doses of SLS > 10(-5) M inhibited cell growth. We conclude that sublethal doses of SLS can stimulate the growth of cultured keratinocytes and fibroblasts. The stimulation of growth seen may be related to the stimulation observed in in vivo irritation.

Cell Count↗
PubMed1993

Percutaneous absorption: a single-layer model.

In vitro percutaneous permeation of betamethasone 17-valerate through excised human skin was studied. Pressure-sensitive silicone adhesive containing betamethasone 17-valerate in suspension was used as a vehicle. Steady-state flux through the split-thickness skin was similar to that through the isolated epidermis. However, the lag-time and half-life after removal of the vehicle were longer for the split-thickness skin than from epidermis. At steady state, 37% of the drug in the split-thickness skin was partitioned in dermis. When the kinetic parameters of a simple single-layer model are defined to specify the permeability coefficient and the drug amount in skin at steady state, this model can predict the longer half-life observed for the split-thickness skin sample compared with that for epidermis. The difference between the observed and theoretical values of the half-life after removal of the vehicle was within 23%. On the other hand, the lag-time had a large variation and the simple diffusion model failed to be predictive. A single-layer model described by two or three kinetic parameters may be able to describe percutaneous permeation kinetics even when the processes after the compound permeation through stratum corneum are not negligible. However, it is stressed that none of the kinetic parameters inherent in this simple model directly represents one of the single physicochemical parameters, such as diffusion and partition coefficients and path length of each skin layer.

Betamethasone Valerate↗