Ignition Delay Studies on Hypergolic Fuel Grains

The ignition delays of several solid hypergolic fuel compositions, casted using various polymeric binders, or as melts, have been determined with fuming nitric acid as oxidizer. The ignition delays of various hypergolic fuel compositions increase drasticaliy on casting with binders like. carboxyl or hydroxyl termninated polybutadiene. Fuel grains cast using some newly syhthesised epoxy  resins with other ingrcdients, such as curing agent, magnesium powder and fuel, have short ignition delays of the order of 200 ms, and also good mechanical strength. Increasing the amount of binder in the composition retards the hypergolicity of the rain. Similar studies have been made on melt-cast systems using low melting hypergolic fuels for casting fuel powders. The ignition delays of the melt-cast grains, are longer than those determined taking the composition in the powder form. The effect of highly hypergolic additives, and metal powders, on the ignition delay of the cast compositions has been determined. Grains having good mechanical strength and short ignition delays have been obtained by optimising the fuel grain composition

Return to fertility after extended chemical castration with a GnRH antagonist

BACKGROUND: Antagonistic analogues of GnRH for the treatment of prostate cancer may be used clinically in persons for whom return to fertility after such treatment is important or desirable. The purpose of this study was, therefore, to evaluate the effects of a long term treatment with orntide, a GnRH antagonist, on testosterone levels and fertility in male rats. METHODS: Two groups of male rats received either 120-day orntide microspheres (8.8 mg orntide/kg/120 days) or vehicle alone (control group). Serum orntide and testosterone levels in both groups were monitored at certain intervals for 9 months from the initiation of treatment. After recovery of normal serum testosterone levels in the treated animals, each rat was housed with two proven breeder, but drug-naive, females. RESULTS: All mates of treated rats achieved pregnancy as rapidly as the mates of control rats although two of the control rats did not sire a litter with either female and one sired only one litter. The mean size of the litters of treated (12.3 offspring per litter) and control (10.6 offspring per litter) were similar. All offspring were grossly normal morphologically and behaviorally during the time to weaning. CONCLUSIONS: These results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist

Preparation and properties of barium sulphate and methyl iothalamate loaded poly(vinyl alcohol) microspheres as radiopaque particulate emboli

Poly(vinyl alcohol) (PVA) microspheres impregnated with barium sulphate and methyl iothalamate, having diameters raning from 100 to 1500 μm were prepared by the glutaraldehyde cross-linking of an aqueous dispersion of PVA containing the radiopaques in paraffin oil using dioctyl sulfosuccinate (DOS) as the stabilizing agent and thionyl chloride as the catalyst. while the use of thionyl chloride allowed the formation of spherical, nonaggregatory beads, other catalysts such as magnesium chloride and hydrochloric acid gave rise to an agglomerated product. The radiopaques were found to be firmly trapped inside the microspheres as they did not leach out on prolonged standing in water, on sonication, or on steam sterilization. Microspheres with pores and channels were also made by incorporating a fine powder of methyl methacrylate along with barium sulphate during their preparation and washing out the polymer after the microspheres were formed. The porous nature of such microspheres was confirmed by transmission electron microscopy (TEM). Microspheres containing the radiopaques exhibited hydrophilicity, swelling ability, and compressibility to a significant extent. the radiopaque nature of the microspheres was confirmed by their x-ray images. In vitro tests using heparinized calf blood showed that the microspheres were nonhaemolytic in nature. These microspheres may find application as radiopaque emboli in particulate embolization

Synthetic hydrogel microspheres as substrata for cell adhesion and growth

Cross-linked poly(methyl methacrylate) (PMMA) microspheres were subjected to alkaline hydrolysis to obtain hydrophilic microspheres having carboxyl residues distributed throughout the matrix. These microspheres were found to support the growth of human skin fibroblasts and human heart and lung cells. Further, fibroblasts grown on them were found to be comparable with those grown on the commercial tissue culture plate with respect to [14C]amino acid uptake and incorporation into proteins. The hydrolyzed PMMA microspheres may find application as a microcarrier for cell culture

Return to fertility after extended chemical castration with a GnRH antagonist

Abstract Background Antagonistic analogues of GnRH for the treatment of prostate cancer may be used clinically in persons for whom return to fertility after such treatment is important or desirable. The purpose of this study was, therefore, to evaluate the effects of a long term treatment with orntide, a GnRH antagonist, on testosterone levels and fertility in male rats. Methods Two groups of male rats received either 120-day orntide microspheres (8.8 mg orntide/kg/120 days) or vehicle alone (control group). Serum orntide and testosterone levels in both groups were monitored at certain intervals for 9 months from the initiation of treatment. After recovery of normal serum testosterone levels in the treated animals, each rat was housed with two proven breeder, but drug-naive, females. Results All mates of treated rats achieved pregnancy as rapidly as the mates of control rats although two of the control rats did not sire a litter with either female and one sired only one litter. The mean size of the litters of treated (12.3 offspring per litter) and control (10.6 offspring per litter) were similar. All offspring were grossly normal morphologically and behaviorally during the time to weaning. Conclusions These results suggest that lack of fertility due to testosterone suppression is reversible after cessation of treatment with this GnRH antagonist.</p

Identification of chemically modified peptide from poly(D,L-lactide-co-glycolide) microspheres under in vitro release conditions

The purpose of this research was to study the chemical reactivity of a somatostatin analogue octreotide acetate, formulated in microspheres with polymers of varying molecular weight and co-monomer ratio under in vitro testing conditions. Poly(D,L-lactide-co-glycolide) (PLGA) and poly(D,L-lactide) (PLA) microspheres were prepared by a solvent extraction/evaporation method. The microspheres were characterized for drug load, impurity content, and particle size. Further, the microspheres were subjected to in vitro release testing in acetate buffer (pH 4.0) and phosphate buffered saline (PBS) (pH 7.2). In acetate buffer, 3 microsphere batches composed of low molecular weight PLGA 50∶50, PLGA 85∶15, and PLA polymers (≤10 kDa) showed 100% release with minimal impurity formation (<10%). The high molecular weight PLGA 50∶50 microspheres (28 kDa) displayed only 70% cumulative release in acetate buffer with significant impurity formation (∼24%). In PBS (pH 7.4), on the other hand, only 50% release was observed with the same low molecular weight batches (PLGA 50∶50, PLGA 85∶15, and PLA) with higher percentages of hydrophobic impurity formation (ie, 40%, 26%, and 10%, respectively). In addition, in PBS, the high molecular weight PLGA 50∶50 microspheres showed only 20% drug release with ∼60% mean impurity content. The chemically modified peptide impurities inside microspheres were structurally confirmed through Fourier transform-mass spectrometry (FT-MS) and liquid chromatography/mass spectrometry (LC-MS/MS) analyses after extraction procedures. The adduct compounds were identified as covalently modified conjugates of octreotide with lactic and glycolic acid monomers within polymeric microspheres. The data suggest that due to steric hindrance factors, polymers with greater lactide content were less amenable to the formation of adduct impurities compared with PLGA 50∶50 copolymers

In vivo release kinetics of octreotide acetate from experimental polymeric microsphere formulations using oil/water and oil/oil processes

The purpose of the present study was to characterize the in vivo release kinetics of octreotide acetate from microsphere formulations designed to minimize peptide acylation and improve drug stability. Microspheres were prepared by a conventional oil/wate (o/w) method or an experimental oil/oil (o/o) dispersion technique. The dosage forms were administered subcutaneously to a rat animal model, and serum samples were analyzed by radioimmunoassay over a 2-month period. An averaged kinetic profile from each treatment group, as a result, was treated with fractional differential equations. The results indicated that poly(l-lactide) microspheres prepared by the o/o dispersion technique provided lower area under the curve (AUC) values during the initial diffusion-controlled release phase, 7.79 ng×d/mL, versus 75.8 ng/sxd/mL for the o/w batch. During the subsequent erosion-controlled release phase, on the other hand, the o/o technique yielded higher AUC values, 123 ng×d/mL, versus 42.2 ng×d/mL for the o/w batch. The differences observed between the 2 techniques were attributed to the site of drug incorporation during the manufacturing process, given that microspheres contain both porous hydrophilic channels and dense hydrophobic matrix regions. An o/o dispersion technique was therefore expected to produce microspheres with lower incorporation in the aqueous channels, which are responsible for diffusion-mediated drug release