M Sznitowska

Medical University of Gdansk, Danzig, Pomeranian Voivodeship, Poland

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Publications (38)80.14 Total impact

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    ABSTRACT: The aim of the work was to quantify possible interactions between surfactants and preserva-tives, comparing surface properties, in model pharmaceutical formulations. Surface parame-ters of 2-component surfactant-preservative a-quous mixtures were determined with a Wil-helmy plate technique, for the so-called principal surfactants (polysorbate 80, egg lecithin, phos-phatidylcholine) and preservatives, which were methylparaben and benzalkonium chloride (BA-C). A generalized surface tension vs. surfactant concentration plot signatures, in the presence of preservative at a fixed amount, allowed: the cri-tical micellar concentration (cmc) shift, additive molecules partition from the surface to the bulk, mixed micelles formation concentration, and ad-ditive surface removal concentration to be de-termined in reference to surface activity of the added substance. Methylparaben is a compound of lower (in comparison to BAC) surface activity, lower partitioning coefficient possessing lower energy and concentration of its removal from the surface, that makes it play effectively an an-timicrobial protection role in the bulk of phar-maceutical products, as already shown by che-mical tests.
    Journal of Biophysical Chemistry 10/2012; 3:324-333.
  • Pawel Stasiak, Marcin Placzek, Przemyslaw Lepek, Malgorzata Sznitowska
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    ABSTRACT: Texture analyzer equipped with mucoadhesive rig has been used for determination of mucoadhesiveness of solid and semisolid drug formulations: lyophilizates, compressed tablets, and gels. Two different mucosa surrogates: mucin solution on a cellulose support and gelatin discs have been employed. The results obtained for different polymers are inconsistent and depend not only on the experimental model but also on the drug formulation. Addition of an excipient (e.g., lactose) or a drug (tramadol HCl, telmisartan) to the lyophilized polymer matrix generally resulted in decrease of observed adhesive forces which depended more on the polymer used than on the composition of the preparation. Due to low predictability of the effect of pharmaceutical formulation (type and composition) on the mucoadhesiveness of the polymer it has been concluded that individually designed experiments have to be applied for each preparation.
    Journal of Dispersion Science and Technology 12/2011; 32(12):1780-1785. · 0.60 Impact Factor
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    Radosław Kraciuk, Malgorzata Sznitowska
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    ABSTRACT: The objective of this study was to investigate the properties of granules and tablets with carbamazepine which were prepared employing a fluidized hot-melt granulation (FHMG) technique. The FHMG process was carried out at 65°C. Macrogol 6000 (PEG 6000) was used as a binder at the content 10% (w/w) of the granulated mass. Granules containing up to 70% (w/w) of the drug and 20-90% (w/w) of a filler (lactose, mannitol, calcium hydrogen phosphate (Di-Cafos), pregelatinized starch, and microcrystalline cellulose (MCC)) were produced. When the drug content was 30% (w/w), the yield of the process was satisfying (>95%) and flowability of the granules was better than placebo granules or drug-loaded granules prepared by wet granulation. Type of a filler had strong impact on physical properties of granules, and size distribution of the particles was the most homogenous when lactose or Di-Cafos were used. The FHMG technique enabled preparation of granules with better compressability compared with the wet-granulated product or with non-granulated powders. Tablets with shorter disintegration time than 10 min were obtained with 2.0% crospovidone added as a disintegrant. In comparison to tablets prepared from the wet-granulated mass, employment of the FHMG method resulted in tablets with faster dissolution of carbamazepine (more than 80% of the drug released within 15 min). This was achieved with mannitol or lactose/MCC, as fillers.
    AAPS PharmSciTech 09/2011; 12(4):1241-7. · 1.58 Impact Factor
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    ABSTRACT: Polymer-drug conjugates have gained significant attention as pro-drugs releasing an active substance as a result of enzymatic hydrolysis in physiological environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a carboxylic acid group-bearing model drug (ibuprofen) was evaluated in vivo as a potential pro-drug for parenteral administration. Two different formulations, an oily solution and an o/w emulsion were prepared and administered intramuscularly (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The concentration of ibuprofen in blood plasma was analysed by HPLC, following solid-phase extraction and using indometacin as internal standard (detection limit, 0.05 microg/ml). No significant differences in the pharmacokinetic parameters (C (max), T (max), AUC) were observed between the two tested formulations of the 3-hydroxybutyric acid conjugate. In comparison to the non-conjugated drug in oily solution, the relative bioavailability of ibuprofen conjugates from oily solution, and o/w emulsion was reduced to 17% and 10%, respectively. The 3-hydroxybutyric acid formulations released the active substance over a significantly extended period of time with ibuprofen still being detectable 24 h post-injection, whereas the free compound was almost completely eliminated as early as 6 h after administration. The conjugates remained in a muscle tissue for a prolonged time and can hence be considered as sustained release systems for carboxylic acid derivatives.
    AAPS PharmSciTech 11/2010; 11(4):1636-41. · 1.58 Impact Factor
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    ABSTRACT: Amorphous paclitaxel dissolves rapidly (1 mg mL(-1)) in an isotonic aqueous dispersion of egg lecithin (5% w/w), a new biocompatible submicron drug carrier consisting of structured aggregates with average size 0.5 microm. The solution is physically stable for at least 24 h and can be administered as an intravenous infusion. After a 5 h infusion in rabbits (0.66 mg kg(-1) h(-1)), changes in blood morphology were comparable to those observed in rabbits that received the commercial product Taxol. No changes in the enzyme profiles (alanine/aspartate aminotransferase or alkaline phosphatase) were observed. However, during infusion of the new formulation plasma concentration of paclitaxel (292 +/- 182 ng mL(-1)) was lower than observed after Cremophor-containing Taxol (540 +/- 262 ng mL(-1)). This result may indicate that the tissue distribution is different for the two drug formulations. Daily intraperitoneal administrations (3 doses/day) in mice demonstrated that the new carrier solution was non-toxic and, relative to Taxol, the new formulation exhibited similar or less toxicity.
    Journal of Microencapsulation 11/2009; 26(7):588-92. · 1.57 Impact Factor
  • Pawel Stasiak, Carsten Ehrhardt, Maria Juzwa, Malgorzata Sznitowska
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    ABSTRACT: A conjugate of ibuprofen with 3-hydroxybutyric acid oligomers has been evaluated as a novel drug delivery model system. This paper focuses on the synthesis and the characterisation of the physicochemical properties of this conjugate, and on hydrolysis studies in aqueous buffers and simulated intestinal fluid. We also describe the development of an analytical method (HPLC) for hydrolysis studies of this compound. The conjugate had high stability in aqueous solutions of pH 6-8 and underwent slow enzymatic hydrolysis. This conjugate is not well suited for oral administration but might be considered a candidate for development of prodrug preparations for parenteral or topical sustained release.
    Journal of Pharmacy and Pharmacology 09/2009; 61(8):1119-24. · 2.03 Impact Factor
  • Krzysztof Cal, Malgorzata Sznitowska, Stanislaw Janicki
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    ABSTRACT: Drug-in-adhesive matrix-type transdermal therapeutic systems for indomethacin (IND) were formulated and evaluated. Silicone and two types of polyacrylates were used as the bases of matrices. Terpinolene was used as a penetration enhancer. The physicochemical properties of matrices were determined. The bioavailability study of IND was performed in rats. The presence of IND in blood was demonstrated for each system. The calculated pharmacokinetics parameters for IND mainly depend on the solubility of IND in the adhesive layer. The positive influence of a penetration enhancer on IND bioavailability was observed only for one type of polyacrylate matrices.
    Drug Development and Industrial Pharmacy 10/2008; 34(10):1125-9. · 1.54 Impact Factor
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    ABSTRACT: Antimicrobial efficacy of methyl and propylparaben combination as potential preservatives for submicron emulsions, and the effect of oil and lecithin concentration on the microbial growth were investigated. Parabens were ineffective in standard or doubled concentrations as per pharmacopoeial criteria. Poor growth inhibition and multiplication of reference strains point to protective and growth properties of submicron emulsions. No correlation was observed between oil/lecithin ratio and efficacy of parabens; partitioning of the latter into the oily phase and lipophilic domains could be the reason for such effect. Further studies are necessary to establish a stable and safe composition of such formulations.
    Drug Development and Industrial Pharmacy 05/2008; 34(4):355-62. · 1.54 Impact Factor
  • Malgorzata Sznitowska, Malgorzata Klunder, Marcin Placzek
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    ABSTRACT: The aim of this study was to find a biocompatible, lecithin-based carrier for paclitaxel (PTX) suitable for intravenous infusion and ensuring a soluble PTX concentration of 100 mg/100 ml or higher for at least 24 h. Aqueous dispersions of egg or soya lecithin (water-lecithin dispersions, WLD), mixed micellar (MM) solutions of egg lecithin and sodium deoxycholate, and formulations containing lecithin plus the co-surfactants and co-solvents poloxamer, polysorbate, Span, benzalkonium chloride, and macrogol were investigated. Amorphous PTX was prepared by lyophilization. PTX co-lyophilized with surfactants was also studied. Unlike crystalline PTX, the drug in an amorphous form is easily soluble in 1-5% (w/w) WLD or in MM. The highest solubility (up to 570 mg/100 ml) was achieved in 5% WLD. Dissolved PTX precipitated from all tested formulations over 24 h. Despite this, concentrations of dissolved PTX of 100 mg/100 ml or higher were observed after 24 h in 5% egg WLD, 1-5% soya WLD, and in 5% MM (lecithin : deoxycholate ratio 1 : 1 w/w). When four different batches of 5% egg WLD were prepared, containing PTX in clinically relevant concentration of 100 mg/100 ml, no precipitation of PTX was observed within 24 h and this formulation is the most promising candidate for further in vivo studies. Neither additional surfactants nor co-lyophilization increased PTX solubility in the lecithin-based carriers. The use of parenteral emulsions as solvents for the co-lyophilized PTX also failed to increase the solubility of the drug up to the target concentration.
    CHEMICAL & PHARMACEUTICAL BULLETIN 02/2008; 56(1):70-4. · 1.56 Impact Factor
  • Dorota Watrobska-Swietlikowska, Malgorzata Sznitowska
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    ABSTRACT: Partitioning of methyl and propyl parabens (methyl and propyl hydroxybenzoate, paraben M and P) between the major phases in the parenteral submicron emulsions was studied. The investigated emulsions contained 10% or 20% soya-bean oil, 1.2% or 2.4% egg lecithin, 0.18% or 0.36% paraben M and 0.02% or 0.04% paraben P. The aqueous phase was obtained by ultracentrifugation, and subsequently, it was subjected to ultrafiltration, which procedure allowed to distinguish between the fractions of free preservatives (Fw) and incorporated in the liposomal or micellar region (Flm). The fractions present in the oily phase and in the interface were calculated. Depending on the formulation, Fw was 17-31% and 2.3-6.0% for paraben M and P, respectively. The Flm values were in a very narrow range, i.e. 3.0-6.0% for both preservatives. Substantial accumulation, i.e. 38-58% was found in the interface and the partitioning into this region was related to the oil/lecithin ratio rather than to lipophilicity of the preservative.
    International Journal of Pharmaceutics 05/2006; 312(1-2):174-8. · 3.46 Impact Factor
  • Justyna Pietkiewicz, Malgorzata Sznitowska, Marcin Placzek
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    ABSTRACT: The aim of the study was to compare incorporation of bupivacaine base, bupivacaine stearate and indomethacin in diluted suspensions of lipospheres (10%, w/w of lipid) and in concentrates (50%, w/w of lipid). The lipid cores were composed of a mixture of solid and liquid triglycerides (Precirol and Miglyol 4:1). The lipospheres sizing between 0.5-10 microm (suspensions) and 0.5-20 microm (concentrates) were prepared using a hot emulsification with high-shear mixing and cold resolidification method. None of the studied drugs was successfully incorporated in the lipid core. The increased incorporation of drugs determined in the concentrated lipospheres was only apparent, since in fact all the dose was only attached to the surface of the lipid particles and was transferred to the aqueous phase in the course of an intensive agitation. The presence of hydrophilic polymers in the aqueous phase did not prevent the expulsion effect although drug precipitation was retarded. The expulsion effect did not correlate with the solubility of drugs determined in the bulk lipids.
    International Journal of Pharmaceutics 04/2006; 310(1-2):64-71. · 3.46 Impact Factor
  • Krzysztof Cal, Katarzyna Kupiec, Malgorzata Sznitowska
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    ABSTRACT: The terpenes disturb lipid arrangement in the intercellular region of the stratum corneum (SC) that leads to the increased permeability of the skin. This effect is used in technology of transdermal drug forms and depends on physicochemical properties of terpenes and their amounts penetrated to the stratum corneum; however terpenes do not need penetrate into viable skin tissue and this event is not even desired. To correlate skin absorption and elimination kinetics of four cyclic terpenes, namely alpha-pinene, beta-pinene, eucalyptol and terpinen-4-ol, applied as neat substance with their physicochemical properties. The terpenes were applied onto the human skin in vitro, and after 1-4 h their content in the separated by a tape-stripping method stratum corneum layers and in the epidermis/dermis was determined using GC. Similarly, the amounts of terpenes in the skin were analysed during 4 h following 1 h absorption. The fastest and progressive penetration into all skin layers was observed for terpinen-4-ol. All studied terpenes are absorbed in the viable epidermis/dermis, however penetration into this layers is time-dependent process, constantly increasing during 4 h. Like for stratum corneum, the largest cumulation in epidermis/dermis was observed for terpinen-4-ol. The elimination of terpenes from the stratum corneum was fast, especially in deeper layers, and much faster if the initial cumulation was small. Investigated cyclic terpenes represent different penetration and elimination characteristics and do not permeate across the skin to the acceptor medium due to large cumulation in the skin tissue. The penetration of terpenes into stratum corneum is greater if their log P-value is close to 3.
    Journal of Dermatological Science 03/2006; 41(2):137-42. · 3.52 Impact Factor
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    ABSTRACT: A dissolution test for oral veterinary pastes with ivermectin using the Ph. Eur. paddle apparatus was developed. Sink conditions were achieved with sodium lauryl sulphate in a concentration of 0.5% as dissolution medium. By means of HPLC fast degradation of ivermectin was observed in HCl 0.1 M solution. Rotation speed of the paddle at 75 rpm was appropriate as demonstrated in a study comparing two different products.
    Pharmazie 11/2004; 59(10):814-5. · 0.96 Impact Factor
  • J Pietkiewicz, M Sznitowska
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    ABSTRACT: Suspensions of lipid microspheres sizing from 1 to 30 microm, whose fluidity and lipid/surfactant composition is suitable for parenteral administration were developed. None of the formulations prepared with Precirol (palmitostearate), as the only lipid, was physically stable during storage, because liquid suspensions formed semisolid gels within one week. Stable 10% (w/w) suspensions of lipid microspheres were produced using saturated triglycerides in combination with medium chain unsaturated triglycerides (Miglyol) as lipids and polysorbate 80 (2% w/w) as a surfactant.
    Pharmazie 05/2004; 59(4):325-6. · 0.96 Impact Factor
  • Krzysztof Cal, Malgorzata Sznitowska
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    ABSTRACT: The purpose of the study was to investigete skin absorption and elimination of three acyclic terpenes: citronellol (C), linalool (L) and linalyl acetate (LA). The pure terpenes were applied onto the human skin in vitro, and after 1-4 h, their content in the stratum corneum layers and in the epidermis/dermis was determined using gas chromatography. Similarly, the amounts of terpenes in the skin were analysed during 4 h following 1-h absorption. Good absorption to the all skin layers was demonstrated as soon as after 1 h: the total skin cumulation of L, LA and C was 827, 124 and 954 microg/cm2, respectively. A self-promoting absorption was observed for L, since the amount of this terpene analysed in the stratum corneum after 1 h was 78.3, rising to 479 microg/cm2 after 4 h. During the elimination phase, a constant drop in the total amount in the skin was observed only for C, while the total skin content of L and LA did not change, although diffusion from the stratum corneum to epidermis/dermis occurred. The log P values of the terpenes were calculated using three different programs, but generally, neither absorption nor elimination can be directly correlated with the physicochemical parameters, despite of the fact that the least absorption was observed for the most lipophilic LA.
    Journal of Controlled Release 01/2004; 93(3):369-76. · 7.63 Impact Factor
  • M Sznitowska, M Płaczek
    Pharmazie 07/2003; 58(6):437-8. · 0.96 Impact Factor
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    ABSTRACT: A 24-h extended-release multiparticulate capsule containing a dose of 500 mg of lithium carbonate divided into 6 tablets 6 mm in size was produced. In order to achieve an immediate and prolonged drug release profile one uncoated tablet and 5 tablets coated with methacrylic acid/ethyl acrylate copolymer Kollicoat MAE30DP were filled into a capsule. The core of tablets consisted of microcrystalline cellulose, lactose, povidone, macrogol and magnesium stearate.
    Bollettino chimico farmaceutico 01/2003; 142(2):69-71.
  • Malgorzata Sznitowska, Ewa A Dabrowska, Stanislaw Janicki
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    ABSTRACT: Aqueous lecithin dispersions (WLD, water-lecithin-dispersion) were obtained by dispersing egg lecithin (1.2 or 2.4% w/w) in an isotonic mixture of glycerol and water. The solubilization potential of the pure phospholipid structures was investigated and compared with that of submicron emulsions containing the same amounts of lecithin and 10 or 20% (w/w) of soya-bean oil. The increase in solubility of the investigated lipophilic drugs in WLD was proportional to the lecithin concentration. Concentration of lecithin in the emulsion was the main factor determining solubility of drugs moderately lipophilic (logP below 2.5), while for more lipophilic compounds the presence of oil was a determinant and for such drugs solubility in submicron emulsion was better than in WLD. WLD obtained in a simple technological process may be considered as a carrier particularly for highly lipophilic drugs: solubility of estradiol in this system was 100-fold higher than in water.
    International Journal of Pharmaceutics 11/2002; 246(1-2):203-6. · 3.46 Impact Factor
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    ABSTRACT: Antimicrobial agents should be added to lecithin-stabilized submicron emulsions when these preparations are non-sterile products or when packed in multidose containers. Eleven antimicrobials were introduced to a standard submicron emulsion. The emulsions were adjusted to pH 5.0 or 8.2 prior aseptic filtration or thermal sterilization, respectively. The physicochemical stability of the preparations was observed during storage for 2 years at room temperature. Parabens showed the best compatibility but satisfying stability was also observed in emulsions containing phenylethanol, m-cresol and benzalkonium chloride. Partitioning studies revealed poor correlation between aqueous solubility and content of the preservatives in the aqueous phase of the emulsion. Only 1.2% of the total content of benzalkonium chloride was found in this phase and incorporation of this compound into different microscopic structures of the emulsion is proposed as a reason for such effect. Preliminary studies on the efficacy of antimicrobial preservation was performed for emulsions containing parabens, benzalkonium chloride or chlorocresol and the negative results bring conclusion that higher concentration of antimicrobials or their combination may be required for efficient preservation of submicron emulsions.
    European Journal of Pharmaceutical Sciences 07/2002; 15(5):489-95. · 2.99 Impact Factor
  • M Sznitowska, S Janicki, A Baczek
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    ABSTRACT: 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.
    Journal of Controlled Release 11/2001; 76(3):327-35. · 7.63 Impact Factor