Renata Jachowicz

Solid dispersion of ketoprofen in pellets.

The formulation of ternary solid dispersions of ketoprofen with Macrogol and kollagen hydrolizate derivative as carriers was elaborated on the basis of the results of the experiments in which different methods of solid dispersion preparation (melting, solvent method, different cooling), different concentrations of drug/carriers and molecular weight of Macrogol were tested. The best solid dispersion consisted of: ketoprofen-Macrogol 6000-KLH(T) (1+8. 9+0.1) was chosen to formulate the pellets on the basis of the pharmaceutical availability of ketoprofen from solid dispersion and the physical chemical studies: thermomicroscopic, DSC and X-ray diffraction. The pellets were prepared by the extrusion and spheronization method. The mechanical properties of the pellets as well as ketoprofen released from pellets containing solid dispersion, in comparison with physical mixtures and the drug alone, were evaluated. The increase in the amount of released ketoprofen from solid dispersion pellets was 3.8-times greater than from the pellets containing the drug alone. The stability of solid dispersion pellets was satisfactory.

The Macromolecular Polymers for the Preparation of Hydrodynamically Balanced Systems—Methods of Evaluation

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 (Ffloat 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 (Tfloat max). HPMC and sodium alginate formulation reached Ffloat 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.

Neural network as a decision support system in the development of pharmaceutical formulation-focus on solid dispersions

The aim of the study was to create simple, neural model of ketoprofen (Ket) dissolution from solid dispersions (SD) and physical mixtures (PM), which could be an aid in prospective development of pharmaceutical formulation. An application of artificial neural networks (ANNs) methodology was investigated using experimental data. Backpropagation (BP) ANNs with two hidden layers, hyperbolic tangent as the activation function and Hampels target function were studied. Neuro-fuzzy systems were also applied. As the input variables formulation type and preparation technology as well as qualitative and quantitative composition of SD and physical mixtures (PM) were selected. Direct incorporation of physicochemical properties of excipients (connectivity index, CI) enhanced ANNs model usability. Further improvement of neural model was achieved by input variables reduction performed on the basis of the sensitivity analysis. ANNs functions as decision support system in prospective ketoprofen SD formulation as well as data-mining tool were confirmed.

Gastroretentive drug delivery systems with L-dopa based on carrageenans and hydroxypropylmethylcellulose.

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 blends 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.

Development of a system for simultaneous dissolution studies and magnetic resonance imaging of water transport in hydrodynamically balanced systems: a technical note.

Summary and ConclusionsWithout disturbing the observed processes, the MRI methods combined with the dissolution studies provide insight into the phenomena occurring when the dosage form comes into contact with aqueous fluids. The MR images allow one to observe the solvent penetration into the hydrophilic matrix and the hydrogel formation. The data obtained in the MRI studies complement information obtained from the dissolution studies. The analysis of MR images may support the explanation of differences in the drug-releasing or floating properties of HBS.

Preformulation Studies on Solid Self-Emulsifying Systems in Powder Form Containing Magnesium Aluminometasilicate as Porous Carrier

The influence of alkaline and the neutral grade of magnesium aluminometasilicate as a porous solid carrier for the liquid self-emulsifying formulation with ibuprofen is investigated. Ibuprofen is dissolved in Labrasol, then this solution is adsorbed on the silicates. The drug to the silicate ratio is 1:2, 1:4, and 1:6, respectively. The properties of formulations obtained are analyzed, using morphological, porosity, crystallinity, and dissolution studies. Three solid self-emulsifying (S-SE) formulations containing Neusilin SG2 and six consisting of Neusilin US2 are in the form of powder without agglomerates. The nitrogen adsorption method shows that the solid carriers are mesoporous but they differ in a specific surface area, pore area, and the volume of pores. The adsorption of liquid SE formulation on solid silicate particles results in a decrease in their porosity. If the neutral grade of magnesium aluminometasilicate is used, the smallest pores, below 10 nm, are completely filled with liquid formulation, but there is still a certain number of pores of 40–100 nm. Dissolution studies of liquid SEDDS carried out in pH = 1.2 show that Labrasol improves the dissolution of ibuprofen as compared to the pure drug. Ibuprofen dissolution from liquid SE formulations examined in pH of 7.2 is immediate. The adsorption of the liquid onto the particles of the silicate causes a decrease in the amount of the drug released. Finally, more ibuprofen is dissolved from S-SE that consist of the neutral grade of magnesium aluminometasilicate than from the formulations containing the alkaline silicate.

Preparation and Evaluation of Piroxicam-HPMCAS Solid Dispersions for Ocular Use

The aim of the study was in vitro evaluation of piroxicam solid dispersions containing hydroxypropyl methylcellulose acetate succinate (HPMCAS-LF, -HF) as a carrier. Binary (piroxicam–HPMCAS) and ternary (piroxicam–HPMCAS–Carbopol 940) solid dispersions were prepared by spray-drying method. The morphological characteristics were investigated by scanning electron microscopy. X-ray diffraction and differential scanning calorimetry were employed to study physical and chemical properties. In vitro release was studied using a flow-through cell technique. Studies of dissolution rate of piroxicam from solid dispersions were carried out in comparison with corresponding physical mixtures and drug alone. The dissolution profiles depend on the presence of Carbopol 940 in solid dispersions.

Physicochemical Properties of Bosentan and Selected PDE-5 Inhibitors in the Design of Drugs for Rare Diseases.

The study provides the physicochemical characteristic of bosentan (BOS) in comparison to tadalafil (TA) and sildenafil citrate (SIL). Despite some reports dealing with thermal characteristic of SIL and TA, physicochemical properties of BOS have not been investigated so far. Recent clinical reports have indicated that the combination of bosentan and PDE-5 inhibitor can improve the effectiveness of pharmacotherapy of pulmonary arterial hypertension (PAH). However, in order to design personalized medicines for therapy of chronic rare diseases, detailed information on the thermal behaviour and solubility of each drug is indispensable. Thus, XRD, DSC and TGA-QMS analyses were applied to compare the properties of the drugs, their thermal stability as well as to identify the products of thermal degradation. The dehydration of BOS started at 70°C and was followed by the chemical degradation with the onset at 290°C. The highest thermal stability was stated for TA, which decomposed at ca. 320°C, whereas the lowest onset of the thermal decomposition process was stated for SIL, i.e. 190°C. The products of the drug decomposition were identified. FT-FIR was applied to study intra- and intermolecular interactions between the drug molecules. FT-MIR and Raman spectroscopy were used to examine the chemical structure of the drugs. Chemoinformatic tools were used to predict the polar surface area, pKa, or logP of the drugs. Their results were in line with solubility and dissolution studies.

Multimodal approach to characterization of hydrophilic matrices manufactured by wet and dry granulation or direct compression methods

PURPOSE OF THE RESEARCH The purpose of the research was to investigate the effect of the manufacturing process of the controlled release hydrophilic matrix tablets on their hydration behavior, internal structure and drug release. Direct compression (DC) quetiapine hemifumarate matrices and matrices made of powders obtained by dry granulation (DG) and high shear wet granulation (HS) were prepared. They had the same quantitative composition and they were evaluated using X-ray microtomography, magnetic resonance imaging and biorelevant stress test dissolution. PRINCIPAL RESULTS Principal results concerned matrices after 2 h of hydration: (i) layered structure of the DC and DG hydrated tablets with magnetic resonance image intensity decreasing towards the center of the matrix was observed, while in HS matrices layer of lower intensity appeared in the middle of hydrated part; (ii) the DC and DG tablets retained their core and consequently exhibited higher resistance to the physiological stresses during simulation of small intestinal passage than HS formulation. MAJOR CONCLUSIONS Comparing to DC, HS granulation changed properties of the matrix in terms of hydration pattern and resistance to stress in biorelevant dissolution apparatus. Dry granulation did not change these properties-similar hydration pattern and dissolution in biorelevant conditions were observed for DC and DG matrices.

Enhanced release of oxazepam from tablets containing solid dispersions

Abstract Solid dispersions of different ratios of Gelita collagel as the carrier and lactose were prepared by the spray drying method. Dissolution studies have shown that by preparing solid dispersions the dissolution rate and the solubility of oxazepam increase markedly, independent of the ratio of drug, carrier and lactose. The properties of the solid dispersions were characterized by X-ray diffraction and polarizing microscopic studies. An amorphous form of all prepared solid dispersions were indicated in X-ray studies. Tablets of solid dispersions of oxazepam/Gelita Collagel, physical mixtures and the drug alone were prepared. The best results from the dissolution test were obtained for tablets containing solid dispersions. They remained in good physical properties when stored for one year in normal conditions.