Effect of crystallinity on electrostatic charging in DPI formulations

Poster Presentation: no. 13PS41Introduction: Many physicochemical, mechanical and environmental factors can influence charging of dry powder inhaler (DPI) formulations - crystallinity is one of these factors. Due to differences in crystal packing and surface energies, there may be differences in charge transfer behaviours between amorphous and crystalline materials. Although the effect of crystallinity on electrostatic charging in DPI formulations has been investigated previously by other researchers, the reported data were inconclusive since the samples not only differed in crystallinity, but also in particle morphology and size distributions. Therefore, these variables are controlled in the present study to determine the role of crystallinity in electrostatic charging of DPI formulations. The objective of this study was to characterize inherent charges generated by amorphous and crystalline micron-sized salbutamol sulfate (SS) powders .....published_or_final_versio

Bioactive proteins and peptides isolated from Chinese medicines with pharmaceutical potential.

Some protein pharmaceuticals from Chinese medicine have been developed to treat cardiovascular diseases, genetic diseases, and cancer. Bioactive proteins with various pharmacological properties have been successfully isolated from animals such as Hirudo medicinalis (medicinal leech), Eisenia fetida (earthworm), and Mesobuthus martensii (Chinese scorpion), and from herbal medicines derived from species such as Cordyceps militaris, Ganoderma, Momordica cochinchinensis, Viscum album, Poria cocos, Senna obtusifolia, Panax notoginseng, Smilax glabra, Ginkgo biloba, Dioscorea batatas, and Trichosanthes kirilowii. This article reviews the isolation methods, molecular characteristics, bioactivities, pharmacological properties, and potential uses of bioactive proteins originating from these Chinese medicines.published_or_final_versio

Pharmacokinetic and pharmacodynamic study of intranasal and intravenous dexmedetomidine

Background: Intranasal dexmedetomidine produces safe, effective sedation in children and adults. It may be administered by drops from a syringe or by nasal mucosal atomization (MAD NasalTM). / Methods: This prospective, three-period, crossover, double-blind study compared the pharmacokinetic (PK) and pharmacodynamic (PD) profile of i.v. administration with these two different modes of administration. In each session each subject received 1 μg kg−1 dexmedetomidine, either i.v., intranasal with the atomizer or intranasal by drops. Dexmedetomidine plasma concentration and Ramsay sedation score were used for PK/PD modelling by NONMEM. / Results: The i.v. route had a significantly faster onset (15 min, 95% CI 15–20 min) compared to intranasal routes by atomizer (47.5 min, 95% CI 25–135 min), and by drops (60 min, 95%CI 30–75 min), (P<0.001). There was no significant difference in sedation duration across the three treatment groups (P=0.88) nor in the median onset time between the two modes of intranasal administration (P=0.94). A 2-compartment disposition model, with transit intranasal absorption and clearance driven by cardiac output using the well-stirred liver model, was the final PK model. Intranasal bioavailability was estimated to be 40.6% (95% CI 34.7–54.4%) and 40.7% (95% CI 36.5–53.2%) for atomization and drops respectively. Sedation score was modelled via a sigmoidal Emax model driven by an effect compartment. The effect compartment had an equilibration half time 3.3 (95% CI 1.8–4.7) min−1, and the EC50 was estimated to be 903 (95% CI 450–2344) pg ml−1. / Conclusions: There is no difference in bioavailability with atomization or nasal drops. A similar degree of sedation can be achieved by either method. / Clinical trial registration: HKUCTR-1617

Pathways of purine ribonucleotide biosynthesis in the adult worm Metastrongylus apri (nematoda: Metastronglyloidea) from pig lung

The pathways of purine ribonucleotide synthesis and interconversion that are operative in the intact adult pig lung worm Metastrongylus apri were identified by radioisotope tracing. The rate of [14C]- glycine incorporation into purines was low but sufficient to demonstrate synthesis de novo. Radioactively labelled adenine, hypoxanthine and guanine were readily taken up and converted to the corresponding mononucleotides. Most of the AMP and GMP formed were phosphorylated to the triphosphates. These two nucleotides were interconvertable by pathways in which IMP is an intermediate. Adenosine was converted to nucleotides by direct phosphorylation as well as via formation of hypoxanthine. The rate of synthesis of adenine nucleotides from hypoxanthine was 5-7 times that of guanine nucleotides; conversion of IMP to AMP and to xanthosine 5′-monophosphate were the rate-limiting steps. © 1981.link_to_subscribed_fulltex

Production of uric acid in the adult lung worm, Metastrongylus apri (nematoda: metastrongyloidea), from pigs

1. 1. Uric acid was found to be a major end product of purine metabolism in adult Metastrongylus apri. 2. 2. The rates of production of radioactive uric acid during the incubation of intact worms with [8-14C]adenine, [8-14C]adenosine, [8-14C]hypoxanthine and [8-14C]guanine were measured. 3. 3. Most of the guanine, adenosine and hypoxanthine were catabolized directly but adenine was first converted to nucleotides before degradation. © 1980.link_to_subscribed_fulltex

Angiostrongylus cantonensis: Characterization of Thymidylate Synthetase

Thymidylate synthetase (TS) is the only enzyme that catalyzes the formation of thymidine nucleotides in Angiostrongylus cantonensis. A fraction enriched in TS was obtained from the gravid nematode by gel filtration and affinity chromatography using methotrexate-agarose. TS, which was well separated from dihydrofolate reductase, has a relative molecular mass of 66 kDa. By electrophoresis in sodium dodecyl sulphate gel, a major protein band corresponding to 31 kDa was observed. This band was shown to be TS by comparing the electrophoretic mobility with an enzyme preparation bound with [6-3H]5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP). Therefore, the enzyme is composed of two identical or very similar subunits. Velocity studies and product inhibition patterns revealed that the TS reaction undergoes a sequential mechanism in which 2'-deoxyuridine 5'-monophosphate (dUMP) is the first substrate added to the active site and thymidine 5'-monophosphate is the last product released. The apparent Km values for dUMP and 5,10-methylenetetrahydrofolate are 10 and 185 microM, respectively. FdUMP and trimethoprim inhibited the parasite TS competitively with dUMP and the Ki values of 23.5 nM and 852 microM, respectively. Methotrexate was a noncompetitive inhibitor of TS. At 0.2 mM 5,10-methylenetetrafolate, 1 mM methotrexate inhibited the activity by 74%.link_to_subscribed_fulltex

Electrostatics in pharmaceutical solids

Pharmaceutical solids are likely to accumulate electrostatic charge through handling processes encountered both in industry and during clinical use. Important advances in the past decade have continued to improve our understanding and enabled better control of electrostatics. Although certain areas have been studied more extensively than others, much remains unexplored at the fundamental level and in vivo deposition studies are required to confirm the impact of charged aerosols in humans. This review has summarised the key fundamentals, highlighted the relevance in industrial and clinical settings, evaluated the factors that influence charging and discussed measurement techniques with regards to pharmaceutical powders. The understanding gained could potentially have regulatory implications, and could assist in the development and manufacture of pharmaceutical powders and their delivery systems. © 2014 Elsevier B.V

Crystallinity and electrostatic charge in inhalable salbutamol sulphate powder aerosols

The Conference program's website is located at http://www.crsaustralia.org/wp-content/uploads/2013/09/Final-Program-V1_31.pd