Formulation and characterization of immediate-release oral dosage forms with zolpidem tartrate fabricated by digital light processing (DLP) 3D printing technique.

The introduction of three-dimensional (3D) printing in the pharmaceutical field has made great strides towards innovations in the way drugs are designed and manufactured. In this study, digital light processing (DLP) technique was used to fabricate oral dosage forms of different shapes with zolpidem tartrate (ZT), incorporated within its therapeutic range. Formulation factors, such as poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 (PEG 400) ratio, as well as water content, were varied in combination with the surface area/volume (SA/V) ratio to achieve immediate drug release. Hypromellose (HPMC) was used as a stabilizing agent of photoreactive suspensions in an attempt to prevent drug sedimentation and subsequent variations in drug content uniformity. Oral dosage forms with doses in the range from 0.15 mg to 6.37 mg, showing very rapid and rapid drug dissolution, were successfully fabricated, confirming the potential of this technique in drug manufacturing with the ability to provide flexible dose adjustments and desirable release profiles by varying formulation factors and geometry of 3D models. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and scanning electron microscopy (SEM) showed that ZT remained in a crystalline form within printed dosage forms and no interactions were found between ZT and polymers.

Quality assessment of total parenteral nutrition admixtures by the use of fractional factorial design.

BACKGROUND/AIM: Parenteral nutrition as a specific as pect of providing nutritients still remains a permanent topic of both theoretical and experimental research. Total parenteral nutrition (TPN) admixtures have complex con tents making difficult to maintain their stability. The most critical parameter is the diameter of a lipid droplet, i.e. droplet size distribution. It is recommended that droplet size should not be more than 5 microm and that the presence of greater droplets should not exceede the value of 0.05%. Lipid droplets size is affected particularly by electrolyte addition, especially polyvalent cations. There is a danger of the added electrolytes interaction with lipid droplets which leads to their aggregation and negative effects upon the admixtures stability. The aim of this study was to as sess the effect of added electrolyte and lipid phase quan tity on the admixture stability. METHODS: Electrolytes were added to the studied admixture of a defined basic formulation contents in accordance with recommenda tions from the literature. Droplets size measurements were performed using the method of laser diffraction with a laser particles analyzer. Effects of independent variables were calculated and evaluated using commercial software. Na(+), K(+), Ca(2+) and Mg(2+) concentrations, as well as the quantity of fat phase were chosen as studied fac tors, i.e. independed variables. The system response, or dependent variable was the median of droplets size. Each of the factors was varied at two levels, higher (+1) and lower (-1), according to the 2(5-2) fractional factorial design. RESULTS: The study suggested the presence of relative uni formity of the results of all the measurements regardless of the quantity of added electrolytes and lipid phase. It was shown that undoubtedly there is the influence of 2 valent cations (calcium and magnesium) upon lipid drop lets size, which is in a direct correlation with theoretical assumption. CONCLUSION: Within a 72-hour testing period there was no significant increase in droplet size, i.e. the studied admixtures remained stable considering droplet size median as the criterion of stability.

[Stability investigation of total parenteral nutrition admixture prepared in a hospital pharmacy].

BACKGROUND/AIM: In the cases when nutrition of patients can not be orally nor enterally performed, parenteral nutrition is a method of the therapy that provides more successful and rapid recovery. In that way, hospitalization can be significantly shorter, healing costs reduced and mortality minimized. Total parenteral nutrition (TPN) admixtures are the most complex systems which contain amino acids, carbohydrates, lipid emulsion, macroelectrolytes (Na+, K+, Ca2+, Mg2+, Cl(-), SO4(2-), PO4(3-)), oligoelements, hydro- and liposoluble vitamines, heparin, insulin and water. Concerning the mentioned complexity, special attention should be payed to physicochemical and microbiological stability of a mixture, because of interactions among components, that can be very hard to analyze. The aim of this study was to investigate the problem of stability of TPN admixtures prepared in a hospital pharmacy. METHODS: Admixture TPN was aseptically prepared in laminar air--flow environment on the basis of the specified order in supplementing components and additives to basic solutions. Solutions were kept in sterile multicompartment ethylene-vinyl-acetate bags. After preparation and slow homogenization, TPN admixtures were submitted to physicochemical and microbiological stability analyses in various period of time. The assessment of physical stability of TPN admixture was done on the basis of visual inspection, determination of pH value and measuring of particle size. The investigation of sterility and pyrogenic test were performed according to Ph. Yug. V regulations. RESULTS: Physico-chemical and microbiological analyses were applied and no significant changes in visual sense, pH value and droplet size stability of the TPN admixture were observed during the period of 60 hours The lipid droplets were smaller in size than 5 microm, that is the most common pharmacopoeia requirement. CONCLUSION: The results of our study confirmed that a TPN admixture prepared in a hospital pharmacy can be stored without stability loss for at least 60 hours.