| Abstrakt: |
Recent research on nanocomposites as potential pharmaceutical carriers, is focused on utilization of inorganic matrices with layered structure in which bioactive molecules/drugs are incorporated. One of the promising inorganic material with such layered structure is clay, which is quite common ingredient in pharmaceutical products, both as excipient or active substance. Clay minerals are not only "inert ingredients", but they can also be used to decrease or increase dissolution rate, delay and/or target drug release, to prevent possible side effects, taste masking or increase stability. Prosperity of clay-based drug delivery systems depends on the amount of a drug retained by the clay, on its release kinetics and on the total amount released during therapeutic regime. Thus, it is very essential to understand and to improve the physico--chemical aspects of drug--clay complexes. The aim of this research is to provide more information on drug-clay stability formulations. Pyrophyllite clay, (Parsovići, Konjic, Bosnia and Herzegovina), Al2Si4O10(OH)2, is a smectite clay type (talc-pyrophyllite group) and was used here as a potential pharmaceutical carrier. Stability of pyrophillite and bioactive molecule/drug was estimated by use of thermal analysis methods (differential thermal analysis/ thermogravimetric analysis - TGA/DTA) and Fouriertransform infrared spectroscopy (FTIR). Additionally detailed kinetic study was done using contemporary kinetic software in order to evaluate kinetics of clay/ bioactive molecule (drug) complex. Antimicrobial study was performed against Staphylococcus aureus (Gram positive bacteria) and Escherichia coli (Gram In epruvetes with 9.9 mL of Muller- Hinton broth and 0.1 mL of bacterial inoculum adjusted to 0.5 McFarland standard was added 1 gram of sterilized pyrophillite. Incubation with 120 rpm shaking was performed during 24h at 37 °C. Decomposition of neat pyrophillite is one-step process with following kinetic triplet: Ea (activation energy) - 216 kJ/mol; A (pre-exponential factor) - 4.1687 x 1010 s-1 and N-th order model, while clay/drug mixture decomposition is a four step process. Third stage in mixture decomposition is of special interest, because decomposition of pyrophillite is happening there. Kinetic parameters for the third stage are as follows: Ea - 176 kJ/mol, A -- 6.537 x 108 s-1 and the N-th order model also gave the best fit. After overnight incubation, we noticed highly significant removing of both bacteria from broth. Staphylococcus aureus was reduced from 2.3 x 109 s-1 cfu/mL to 5.5 x 106 s-1 cfu/mL, while Escherichia coli was reduced from 4.5 x 1011 s-1 cfu/mL to 3.5 x 108 s-1 cfu/ mL. Based on the kinetic results we can conclude that thermal stability of pyrophillite is slightly lowered comparing to neat pyrophillite data, but on the other hand pyrophillite did not make any impact on thermal stability of other components in mixture. This information is of great interest for stability assessment of clay/drug mixture. [ABSTRACT FROM AUTHOR] |
