摘要:

AbstractA fracture mechanics approach has been adopted to show that the addition of polymeric binders to a wet powder mass reduces the brittleness of the dried mass.The amount of reduction is dependent on the type of polymer and the concentration of polymer in solution.The approach offers a method of choosing binders for granulation procedures.

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00733.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractA plot of the mole fraction solubility against the Hildebrand solubility parameter of solvent mixtures sometimes shows two solubility maxima—the chameleonic effect. In this work we describe two computer‐optimized equations for predicting solubility of drugs in binary solvent mixtures showing two solubility maxima at ambient and different temperatures.The accuracy of the model expressing solubility at the ambient temperature was a factor of two better than that of a previous model and the fitness of data to the novel equation describing solubility at different temperatures was also g

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00734.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe aim of this work was to investigate whether the interaction between sodium dodecyl sulphate (SDS) and celluloses would alter the swelling behaviour of hydroxypropylmethylcellulose matrices. A simple weight change method was employed to follow the swelling process.The extent of swelling of hydroxypropylmethylcellulose matrices was found to be reduced when sodium dodecyl sulphate was added to the surrounding fluid. Previous studies in the pharmaceutical literature have centred on the role of salt formation between SDS and cationic drugs as the controlling factor in limiting dissolution. However, the changes in swelling behaviour in the presence of SDS indicates that poorly soluble drugs could have their dissolution profiles affected by the presence of SDS due to the surfactant cellulose interaction.

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00735.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractGastric mucus, obtained from various sources has been used in many bioadhesion studies, particularly those concerning rheological synergism between mucus and putative mucoadhesives. This study used dynamic oscillatory rheology to compare the behaviour of commercially obtained mucins with mucin samples prepared directly from porcine stomachs, with regard to their use in rheological studies of bioadhesion.All commercial mucins were found to be viscous sols, giving mechanical spectra typical of dilute polymer solutions with a non‐ordered polymeric structure rather than the typical viscoelastic behaviour of native mucus, even at concentrations far in excess of those seen in‐vivo. Homogenized mucus, containing protease inhibitors, behaved like a viscoelastic gel, giving tan δ values<1, while a crude mucus sample showed markedly less gellike properties, presumably as a result of degradation processes that had occurred before testing.It was concluded that the homogenized mucus sample was the best rheological model for a mucus gel, and will be used in all further studies. Commercially obtained mucins showed little similarity to native mucus in their behaviour, and are therefore inappropriate models for use in rheological investigat

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00736.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractPorous sol‐gel glass was used as a prolonged delivery system for progesterone.Cylindrical rods doped with [3H]progesterone were implanted subcutaneously into adult male Wistar rats. The release rate was determined by measuring the blood radioactivity using scintillation technique. The implants were removed from the animals and put into pure alcohol to determine the amount of steroid remaining in the sol‐gel glass. It was found that following a short initial burst effect, the release rate was nearly constant for over four weeks.The results suggest that the design of the porous sol‐gel glass implants described in this study provides a useful method for prolonged delivery of progest

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00737.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractSalbutamol urinary excretion 0.5 h post inhalation has been shown to represent the relative bioavailability to the lungs from an inhaled dose, while that of salbutamol and its metabolite over 24 h reflects the total systemic bioavailability. We have used this method to compare the Cyclohaler using Cyclocaps (Pharbita Ltd, UK) with the Rotahaler using Ventolin Rotacaps (Allen&Hanburys Ltd, UK).Nine healthy volunteers trained in inhaler technique (mean ± s.d. age of 26.1 ± 7.3 years; weight 66.6 ± 9.4 kg), inhaled 200 μg salbutamol using the Cyclohaler and the Rotahaler in a random order at intervals of one week. Urine collections were made at 0.5 h and pooled up to 24 h post inhalation. The mean (s.d.) salbutamol excreted 0.5 h post inhalation using the Cyclohaler and Rotahaler was 4.44 (1.95) and 2.33 (1.17) 4mUg, respectively. The 0.5/24 h Cyclohaler to Rotahaler ratio mean (95% confidence interval) was 192.9 (52.9, 332.8)%. The Cyclohaler delivers more salbutamol to the lungs than the Rotaha

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00738.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe ester prodrugs of menahydroquinone‐4 (menahydroquinone), the active form of menaquinone‐4 (menaquinone, vitamin K2(20)), were identified in previous reports as prodrugs that could achieve the systemic liver‐specific delivery of menahydroquinone. The present study was undertaken to investigate the mechanism of the prodrugs for vitamin K‐dependent carboxylation and their action in the warfarin‐poisoned rat liver.A rat liver microsomal test system for assessing the carboxylation mechanism of the prodrugs was developed. In this system, the pathways for cleavage (hydrolysis) of the prodrug and for the reductive activation of menaquinone can be provided, and the vitamin K‐dependent carboxylase can accept the synthetic tripeptide BOC‐Glu‐Glu‐Leu‐OMe as substrate. With this system, the carboxylation stimulated with the prodrugs and the enzymatic cleavage of the prodrugs were determined. The prodrug could stimulate the carboxylase activity in the absence of dithiothreitol, an artificial activator of the reductive activation pathway of menaquinone, and the activity order was as follows: 1‐monoester>1,4‐bisester>4‐monoester. The carboxylation activities of the prodrugs were in the same order as the liver microsomal enzymatic reconversion characteristics of the prodrugs. The carboxylation activity of the selected prodrug (1‐monoester) was strongly inhibited in the presence of eserine, a carboxylesterase inhibitor. The prodrug could also stimulate the carboxylase under warfarin‐poisoning conditions, where the vitamin K cycle was strongly inhibited.The results confirmed that the prodrugs could generate menahydroquinone in the active site, and that the resultant menahydroquinone could act as cofactor for the carboxylase without reductive activation processes of menaquinone to menahydroquinone. Such bioreductive activation‐independent vitamin K‐dependent carboxylation characteristics of the prodrugs leads to enhanced pharmacological efficacy in the treatment of hypoprothrombinaemia induced in patients undergoing cou

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00739.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractElcatonin, used for treatment of hypercalcaemia, Paget's disease and osteoporosis, causes nausea and flushing of the face and hands. To determine whether this was because of increased levels of 5‐hydroxytryptamine (5‐HT), the effect of elcatonin on the plasma levels of 5‐HT was studied in five healthy volunteers.After a single intramuscular administration of elcatonin (20 int. units), peak plasma elcatonin levels were achieved 30 min after injection. Plasma 5‐HT concentrations rose similarly with about 1.4‐fold increase after 30–45 min, while plasma levels of vasoactive intestinal peptide but not substance P nor calcitonin gene‐related peptide increased about fivefold after elcatonin injection. Oral pretreatment with granisetron, a selective antagonist of 5‐HT3receptor, significantly reduced elcatonin‐elevated vasoactive intestinal peptide, release and the extent of side‐effects such as cutaneous flushing (most obvious in the face and hands).These results suggest that 5‐HT seems to be closely associated with the side‐effects of elcatonin, mediating a release of vasoac

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00740.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractThe effect of the sialogogue, anethole trithione, on saliva levels of neuropeptide substance P was studied in five healthy volunteers.Peak saliva substance P level (approx. 23 fmol mL−1) was achieved 10 min after lunch and then declined to baseline (approx. 9 fmol mL−1) within 60 min. After a single oral administration of anethole trithione (25 mg), peak plasma anethole trithione level (approx. 1.1 ng mL−1) was achieved at 120 min after administration. Saliva substance P concentrations rose similarly with peak level (approx. 15 fmol mL−1) 60 to 240 min after anethole trithione administration, whereas plasma substance P levels did not change significantly.Substance P nerve in the salivary gland may be involved in the enhancement of the salivary secretion by anethole trithione tr

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00741.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractIntrathecal administration of the calmodulin inhibitors W‐7 and calmidazolium has been shown to produce analgesia in the rat formalin test. The pain intensity of both the first phase and the initial period of the second phase are antagonized by these drugs. We now further characterize the effect of intrathecal W‐7 (1 μmol) on the second phase of the formalin test.In a low‐intensity formalin test (1% instead of the standard 2.5%), the analgesic effect of W‐7 persisted throughout the second phase, showing that the analgesic effect is dependent on the intensity of noxious stimulation. In a standard formalin test, W‐7 injected 5 min—but not 20 min—after formalin, reduces the intensity of the second phase.Thus, W‐7 directly blocks the induction of the second phase but does not modify

ISSN:1460-8081    

DOI:10.1111/j.2042-7158.1996.tb00742.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY