Dry Dosage Form Research Articles

Process and formulation parameters influencing the survival of Saccharomyces cerevisiae during spray drying and tableting

Probiotic microorganisms provide health benefits to the patient when administered in a viable form and in sufficient doses. To ensure this, dry dosage forms are preferred, with tablets in particular being favored due to several advantages. However, the microorganisms must first be dried as gently as possible. Here, the model organism Saccharomyces cerevisiae was dried by spray drying. Various additives were tested for their ability to improve yeast cell survival during drying. In addition, the influence of various process parameters such as inlet temperature, outlet temperature, spray rate, spray pressure and nozzle diameter was investigated. It was possible to dry the yeast cells in such a way that a substantial proportion of living microorganisms was recovered after reconstitution. Systematic variation of formulation and process parameters showed that the use of protective additives is essential and that the outlet temperature determines the survival rate. The subsequent compression of the spray-dried yeast reduced viability and survival could hardly be improved by the addition of excipients, but the tabletability of spray-dried yeast protectant particles was quite good. For the first time, loss of viability during compaction of spray-dried microorganisms was correlated with the specific densification, allowing a deeper understanding of the mechanism of cell inactivation during tableting.

Spray Drying and Particle Engineering in Dosage Form Design for Global Vaccines.

Vaccines are a very important tool in the effort to reduce the global burden of infectious diseases. Modern vaccines can be formulated in several ways to induce specific immunity, including through the use of live bacteria, subunit antigens, and even genetic material. However, vaccines typically need to be transported and stored under controlled refrigerated or frozen conditions to maintain potency. This strict temperature control is incompatible with the available infrastructure in many developing countries. One method of improving the thermostability of a vaccine is through drying of a liquid presentation into a dry dosage form. In addition to enhancing the capability for distribution in resource-poor settings, these dry vaccine forms are more suitable for long-term stockpiling. Spray drying is a drying method that has been successfully used to stabilize many experimental vaccines into a dry form for storage above refrigerated temperatures. Additionally, the use of spray drying allows for the production of engineered particles suitable for respiratory administration. These particles can be further designed for increased out-of-package robustness against high humidity. Furthermore, there are already commercial dry powder delivery devices available that can be used to safely deliver vaccines to the respiratory system. The research in this field demonstrates that the resources to develop highly stable vaccines in flexible dosage forms are available and that these presentations offer many advantages for global vaccination campaigns.

Biotechnological approaches to the use of glauconite in agriculture

We studied the efficiency of glauconite use as a natural sorbent in soils contaminated with heavy metals, as well as the possibility of its use as a natural mineral fertilizer. It has been shown that the addition of glauconite to soil contaminated with lead acetate and zinc sulfate leads to an increase in the total microbial number, micromycetes, actinomycetes and nitrogenfixing bacteria. They are determined main parameters of immobilization Agrobacterium radiobacter 204, Rhizobium leguminosarumbiovartrifoli, Flaviobacteriumfulvum L 30 on glauconite to create dry dosage forms of Biologicals. It was found that when creating dry dosage forms of biological product, the optimal ratios in the system of “biomass:glauconite” are 1:2 and 1:4 when dried for 24 hours at 22-24°C. Introduction of the developed method of immobilization will help toprolong the viability of microorganisms in the biological product at the required level for 4 months.

Ferum in the content of feed additives, prepared feeds and premixes on the pharmaceutical market in Ukraine

The article presents the results of researches of the national market of feed additives, prepared feeds and premixes containing Ferum, registered in Ukraine (by the date 1.03.2018). It has been established that, unlike complexes of iron and dextran in the form of injectable solutions, such pharmaceutical products as feed additives, ready-made fodders and premixes containing Ferum are characterized by a variety of release forms for different species of animals and birds. The number of such products is 55, among them 14 items (26%) are products of production of Ukraine, while this pharmaceutical product for poultry is offered mainly by Polish manufacturers. The market of this group of products for small animals is characterized by a large variety of flavoring properties and forms of release: tablets, powders, granules, flakes, jelly or lime slices, etc. There are only three producers of Ukraine of such pharmaceutical products in the Ukrainian market, while the largest number is offered by companies of Germany and Czech Republic. In addition, the company Vita Traat (Germany) offers vitracraft in the form of pellets as a feed for decorative chinchillas. In the pharmaceutical market of complexes of feed additives, prepared feeds and premixes containing Ferum for various types of animals and poultry. There is a trend that manufacturers, in addition to the specifics of the species, age, physiological processes, and for products for dogs and cats their breed too, take into account the modern needs of the ukrainian consumers, for example, Cargill Poland Sp., Department of Kishkovo, Plant of Premixes of the LNB (Poland) exports to Ukraine 5 types of premixes for broilers. The range of feed additives, ready forages and premixes containing Ferum for bovine animals is less varied, but besides the dry dosage forms, there is a feed additive for calves in the form of calf id peas (Inform Nutrishin Island, Ltd., Ireland). In addition, iron is a part of the substitute of milk for calves. In the national market, there are also Ferum-containing feed additives for animals of different species, which are available in the form of solutions for oral use.

Oral Delivery of Probiotics in Poultry Using pH-Sensitive Tablets.

As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.

Preformulation studies of ceftriaxone for pediatric non-parenteral administration as an alternative to existing injectable formulations

Ceftriaxone, a third generation cephalosporin, has a wide antibacterial spectrum that has good CNS penetration, which makes it potentially suitable for initial treatment of severe neonatal pediatric infections providing suitable formulation. We evaluated its physicochemical and technical characteristics to assess its potential for development as a non-parenteral dosage form. As ceftriaxone is marked only for injectable use, these data are not available. Using HPLC and Karl Fischer titration, sensitivity of ceftriaxone to water, feasibility and impact of pharmaceutical processes and compatibility with common pharmaceutical excipients were assessed. X-ray diffraction studies gave deeper insight into the mechanisms involved in degradation. Chemometrical analysis of near infrared spectra enabled classification of ceftriaxone powder according to exposure conditions or processes applied. The results showed that ceftriaxone was not highly hygroscopic, could be processed in all climatic zones, but should be packaged protected against humidity. Controlling water presence in formulation was shown critical, as ceftriaxone degraded in the presence of water content above 2.4% w/w. To improve flowability, a critical parameter for dry dosage form development, granulation (wet and dry techniques, providing complete drying and moderate force compaction respectively) was shown feasible. Compression with moderate forces was possible, but grinding and high compression forces significantly affected long term ceftriaxone stability and should be avoided. Based on these results, development of ceftriaxone non-parenteral solid or liquid non-aqueous forms appears feasible.

Cabozantinib Loaded DSPE-PEG2000 Micelles as Delivery System: Formulation, Characterization and Cytotoxicity Evaluation

Cabozantinib, a potent pan-tyrosine kinase inhibitor, has been reported to provide enhanced antitumor efficacy by simultaneously inhibiting both MET and VEGF pathways, which are critical to tumor angiogenesis, survival and migration. It's very poor water solubility prevents its administration by the intravenous route, which may be important in patients unable to take the drug orally. In this study, we developed an efficient PEG-lipid-based polymeric micelle formulation with enhanced drug solubility and stability for cabozantinib delivery. DSPE-PEG2000 micelles encapsulating cabozantinib were prepared by a thin-film rehydration method followed by a lyophilization process to generate the dry dosage form. The average hydrodynamic diameter of freshly prepared micelles was 11 nm with a narrow size distribution, and the dry micelle cake could be fully reconstituted by rehydration. Approximately 75% of the drug was encapsulated into the lyophilized cake, and a sustained drug release profile was observed in simulated normal physiological release medium. Compared with the free cabozantinib solution, the drug-loaded micelles displayed significantly enhanced intracellular accumulation and cytotoxicity in human glioblastoma cancer cells and non-small lung cancer cells. These results suggest that the micellar formulation of cabozantinib may serve as a promising nanocarrier in anticancer treatments.

Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles

β-casein is an amphiphilic protein that self-organizes into well-defined core–shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads >100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which >95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration.

Mucoadhesive Microparticles in a Rapidly Dissolving Tablet for Sustained Drug Delivery to the Eye

To test the hypothesis that mucoadhesive microparticles formulated in a rapidly dissolving tablet can achieve sustained drug delivery to the eye. Mucoadhesive microparticles, smaller than 5 μm were fabricated with poly(lactic-co-glycolic acid) and poly(ethylene glycol) as a core material and mucoadhesion promoter, respectively, and encapsulated pilocarpine as a model drug. These microparticles were embedded in a poly(vinyl alcohol) matrix to form a dry tablet designed to reduce rapid clearance of the microparticles on initial application to the eye. This in vitro drug release study exhibited that for all formulations, approximately 90% of pilocarpine was released during the first 10 minutes, and the remaining 10% was released slowly for 3 hours. In vivo mucoadhesion test on the rabbit eye indicated that mucoadhesive microparticles adhered significantly better to the preocular surface than other formulations. To assess the pharmacodynamics, the most prolonged pilocarpine-induced pupil constriction was observed in rabbit eyes in vivo using a tablet with mucoadhesive microparticles; it lasted up to 330 minutes. The authors conclude that mucoadhesive microparticles formulated into a dry dosage form is a promising system for sustained drug delivery to the eye.

Development of tablets containing probiotics: Effects of formulation and processing parameters on bacterial viability

The probiotic products available in the market nowadays are mostly in the form of liquid or semisolid formulations which show low cell viability after oral administration, mainly because the bacteria do not survive the harsh conditions in the stomach. The development of suitable dry dosage forms enable higher bacterial survival and consequently is the main aim of the present study. An anticipated advantage is that due to the low water-activity lyophilized bacterial cells will preserve their viability. Further, by a proper selection of a tablet forming matrix, it is foreseen that the entrapped bacteria are protected against the low pH in the stomach. In this study, the effects on bacterial survival in tablets were investigated concerning compression force, matrix forming excipients such as hydroxypropyl methylcellulose phthalate (HPMCP) or other swelling agents. The results showed that the proportion of matrix forming excipients in tablets and the compression force affected the properties of probiotic tablets in terms of tensile strength and disintegration as well as the survival of the bacteria. The tensile strength of the tablets increased with increase of HPMCP content. Tablets manufactured with high compression force showed a slow disintegration time and high bacterial cell viability (more than 80%). Incorporation of sodium alginate in the tablets resulted in higher cell survival in simulated GI fluid (>90%) and a suitable disintegration time (approximately 5 h). By a proper design of the formulation, tablets with a fast disintegration time and a high preservation of bacterial cell viability were developed.

新規抗生物質E1040の固体安定性と製剤化研究について

In designing the dosage form, one major factor controlling their physicochemical properties is solid forms of the drug powder. The method for improving the physicochemical stability of unstable beta-lactam antibiotics is very important. E1040 is a novel parenteral 3-betaine type cephalosporin which has a broad antibacterial spectrum and potent activities against Citrobacter, freundii, Enterobacter cloacase, and glucose-non-fermentative bacteria, including P. aeruginosa. The present study was intended to provide the solid-state chemical stability of perenteral steril dry dosage form of E1040. The chemical stability differences among the various solid forms, dry amorphous, additive freeze dried amorphous solid and crystalline powder, were evaluated as a function of temperature by thermo stress tests. Freeze dried anhydrous amorphous form was the first steril dry dosage form investigated during the preformulation study. However, this compound is chemically unstable, in the titer of them, reduction are observed in the freeze dried amorphous solid. In order to select the most suitable solid form of E1040, two methods were used. One was crystalline solid and the other was NaCl additive freeze-dried formulation. Through our experiments, the solid-state chemical stabilization can be achieved by these two methods (effect of crystal structure and effect of NaCl additive).