PRELIMINARY STUDY OF INSULIN DRY POWDER FORMULATION: CRITICAL PROCESS PARAMETERS ON SPRAY-FREEZE-DRYING AND CRITICAL MATERIAL ATTRIBUTE OF TREHALOSE AND INULIN AS STABILIZER

Objective: The aim of this study was to obtain recommendations about critical process parameters (CPP) and optimal ratio of trehalose and inulin as critical material attribute (CMA) on insulin dry powder formulation with spray-freeze-drying (SFD) method. Methods: Inulin dry powder was formulated with the SFD method, which consisted of an atomization process and freeze-drying (FD). SFD processes were optimized in order to obtain dry powder and CPP was analyzed. All seven variations of formulas proceeded with physicochemical characterization to obtain the optimal formula. Results: In the early optimization, there was a slight time lag between the atomization process and FD; as a result, some of the powder coagulated and crystallized. Another critical parameter was that the FD process should not be interrupted for at least 50 h of FD. Dry powder proceeded with physicochemical characterization, a formula without inulin showed semicrystalline properties, while six formulas had amorphous properties due to its combination. All formulas had a spherulite shape and rough surface. Five formulas with the combination of trehalose and inulin obtained dry powders with a diameter range of 30-43 μm, moisture content below 3.5% and high encapsulation efficiency (EE). Formula with the ratio of 1:1 (F4) showed optimal properties with moisture content and EE of 2.62% and 99.68%, respectively. Conclusion: This study concluded that there were two critical process parameters in the SFD method. There should be no time lag in SFD process and FD time which should not be interrupted. The optimal ratio for trehalose and inulin was shown by F4 with ratio of 1:1.

Anthocyanin content and storage stability of spray/freeze drying microencapsulated anthocyanins from berries: a review

A comprehensive literature search for articles published on spray and freeze-dried anthocyanins from a large variety of berries was performed. Out of a total of two-hundred and eight collected values, anthocyanin content in encapsulates had a 120-fold variation depending on the raw material and type of encapsulating agents. Highest observed anthocyanin concentration amounted to about 3500 mg/100 g powder. In most cases increasing the amount of encapsulant agents led to a noticeable reduction in the concentration of anthocyanins, this being attributable to a predominance of the dilution effect. Retention of encapsulated anthocyanins after storage at 25 °C (in darkness) for periods between 90 and 180 days were in the range of 80–67%, as long as the water activity (aw) was 0.33 or less. Some predicted values of half-time (t1/2) from literature must be taken with precaution since in many cases they were derived from experimental measurements taken at storage times smaller than predicted half times. Anthocyanin degradation during storage occurred even below the glass transition temperature (Tg) of the amorphous matrices.

Post-Processing Techniques for the Improvement of Liposome Stability

Liposomes have been utilized as a drug delivery system to increase the bioavailability of drugs and to control the rate of drug release at the target site of action. However, the occurrence of self-aggregation, coalescence, flocculation and the precipitation of aqueous liposomes during formulation or storage can cause degradation of the vesicle structure, leading to the decomposition of liposomes. To increase the stability of liposomes, post-processing techniques have been applied as an additional process to liposomes after formulation to remove water and generate dry liposome particles with a higher stability and greater accessibility for drug administration in comparison with aqueous liposomes. This review covers the effect of these techniques including freeze drying, spray drying and spray freeze drying on the stability, physicochemical properties and drug encapsulation efficiency of dry liposomes. The parameters affecting the properties of liposomes during the drying process are also highlighted in this review. In addition, the impact of using a protective agent to overcome such limitations of each process is thoroughly discussed through various studies.

Intratracheal inoculation of AHc vaccine induces protection against aerosolized botulinum neurotoxin A challenge in mice

Botulinum neurotoxin (BoNT), produced by Clostridium botulinum, is generally known to be the most poisonous of all biological toxins. In this study, we evaluate the protection conferred by intratracheal (i.t.) inoculation immunization with recombinant Hc subunit (AHc) vaccines against aerosolized BoNT/A intoxication. Three AHc vaccine formulations, i.e., conventional liquid, dry powder produced by spray freeze drying, and AHc dry powder reconstituted in water are prepared, and mice are immunized via i.t. inoculation or subcutaneous (s.c.) injection. Compared with s.c.-AHc-immunized mice, i.t.-AHc-immunized mice exhibit a slightly stronger protection against a challenge with 30,000× LD50 aerosolized BoNT/A. Of note, only i.t.-AHc induces a significantly higher level of toxin-neutralizing mucosal secretory IgA (SIgA) production in the bronchoalveolar lavage of mice. In conclusion, our study demonstrates that the immune protection conferred by the three formulations of AHc is comparable, while i.t. immunization of AHc is superior to s.c. immunization against aerosolized BoNT/A intoxication.

Comparison of Flowability and Sinterability Among Different Binder Jetting Feedstock Powders: Nanopowder, Micropowder, and Granulated Powder

Feedstock powders used in binder jetting additive manufacturing include nanopowder, micropowder, and granulated powder. Two important characteristics of the feedstock powders are flowability and sinterability. This paper aims to compare the flowability and sinterability of different feedstock powders. Three powders were compared: nanopowder (with a particle size of ∼100 nm), micropowder (with a particle size of 70 μm), and granulated powder (with a granule size of ∼70 μm) made from the nanopowder by spray freeze drying. Flowability metrics employed included apparent density (AD), tap density (TD), volumetric flow rate (VFR), mass flow rate (MFR), Hausner ratio (HR), Carr index (CI), and repose angle (RA). Sinterability metrics employed included sintered bulk density (SBD), volumetric shrinkage (VS), and densification ratio (DR). Results show that the granulated powder has a higher flowability than the nanopowder and a higher sinterability than the micropowder. Moreover, different flowability metric values of the granulated powder are close to those of the micropowder, indicating that these two powers have a comparably high flowability. Similarly, different sinterability metric values of the granulated powder are close to those of the nanopowder, indicating that these two powders have a comparably high sinterability.