ABSTRACT
Taurine, the most abundant free amino acid in leukocyte cytosol traps hypohalous acids (HOCl and HOBr) to produce N-chlorotaurine (taurine chloramine, NCT and N-bromotaurine (taurine bromamine, Tau-NHBr,) respectively. Both haloamines show anti-inflammatory and antimicrobial properties. However, the therapeutic applicability of Tau-NHBr is limited due to its relatively poor stability. To overcome this disadvantage, we have synthesized the stable N-bromotaurine compounds N-monobromo-2,2-dimethyltaurine (Br-612) and N-dibromo-2,2-dimethyltaurine (Br-422). The aim of this study was to compare anti-inflammatory and microbicidal properties of Br-612 and Br-422 with that of Tau-NHBr and bromamine T (BAT). We have shown that all the tested compounds show similar anti-inflammatory properties. Importantly, the stable N-bromotaurine compounds exerted even stronger microbicidal activity than Tau-NHBr. Finally, for the purpose of topical application of these compounds we have developed a carbomer-based bioadhesive solid dosage form of BAT and Br-612, featuring sustained release of the active substance.
Subject(s)
Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Bromides/pharmacology , Taurine/pharmacology , Animals , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Drug Stability , Mice , Sulfonamides/pharmacologyABSTRACT
A comprehensive study was conducted to investigate the effects of carrageenans, and hydroxypropylmethylcellulose (HPMC) on the properties of hydrodynamically balanced systems (HBS) containing L-dopa as a model drug. The novel integrated approach included measurements of: solvent uptake, erosion, apparent density and changes in the internal structure of dosage forms during dissolution test by means of a USP4 compatible MRI. Differences in water ingress into the matrices with pure carrageenans (ι, κ, λ) or low viscous HPMC, were detected by non-invasive magnetic resonance imaging. Matrices based on carrageenans subjected to rapid hydration and erosion, were not able to maintain satisfactory floating properties for a sufficiently long period of time. The application of carrageenans in mixtures with HMC promoted water uptake by HBS formulations. The effect produced by varying the polymer blend's composition on release of the L-dopa was also studied. Dissolution data was fitted to Korsmeyer-Peppas equation. For matrices containing mixtures of carrageenan and HPMC, the linear increase in the releasing rate constant, K, with the carrageenan content in the matrix was observed.
Subject(s)
Carrageenan/chemistry , Drug Carriers , Levodopa/administration & dosage , Methylcellulose/analogs & derivatives , Administration, Oral , Chemistry, Pharmaceutical , Dosage Forms , Drug Compounding , Hypromellose Derivatives , Kinetics , Levodopa/chemistry , Linear Models , Magnetic Resonance Imaging , Methylcellulose/chemistry , Models, Chemical , Solubility , Stomach , Technology, Pharmaceutical/methodsABSTRACT
Evaluation of macromolecular polymers used as excipients for the preparation of hydrodynamically balanced systems (HBS) was carried out. Hard gelatine capsules were filled with polymeric substances belonging to various chemical groups (chitosan, sodium alginate, hydroxypropylmethycellulose--HPMC). The following properties of the HBS were investigated: density, hydration, erosion and floating force. The solvent penetration process into the HBS was visualized using magnetic resonance imaging (MRI) technique. Densities of the HBS in hydrochloric acid (0.1 M) ranged from 0.37 g/cm3 to 0.71 g/cm3. Each polymer demonstrated different hydration/erosion abilities and floating properties. The maximum floating force (F(float max)) for capsules size 0, ranged from 26.7 mN (sodium alginate) to 64.7 mN (chitosan). HBS formulations also varied in time to reach maximum floating force (T(float max)). HPMC and sodium alginate formulation reached F(float max) within half an hour after immersion, while in the case of chitosan formulations (deacetylation degree (d.d.) 66% and d.d. 93%), the time was 184 minutes and 218 minutes respectively. The floating properties of the dosage forms were reliant on type of the polymer and the medium-fasted state simulated gastric fluid (FaSSGF) or fed state simulated gastric fluid (FeSSGF). The size of the HBS influenced the floating force value. The mechanisms of erosion and swelling of the polymeric matrices play a dominant role in flotation of the dosage forms.