Biomedical subjects

M Hindle

Publications and source records attributed to M Hindle.

9 recordsLinked to original sources

PubMed2004

Effect of energy on propylene glycol aerosols using the capillary aerosol generator.

The CAG is being developed for pulmonary drug delivery. Liquids are pumped, heated and vaporized by the CAG, whence they nucleate and condense to form aerosols. This study characterized the effect of energy on the aerosolization process. With increasing energy, the CAG produced an increasing fine particle fraction (FPF) until "optimal aerosolization" was achieved between 40 and 45 J; this energy range agreed with that theoretically required to vaporize the dose of PG. Further increases in energy above this optimal range did not improve PG's aerosolization efficiency. Based on the energy, FPF and temperature profiles, it was possible to deduce the nature of the liquid flow-boiling during aerosol generation. The aerosol particle size went through a minimum, as energy was increased through the "optimal range." In the "energy excess" region, where additional energy increased PG vapor temperature and velocity, droplet sizes were increased primarily due to changes in the nucleation rates and supersaturation ratios affecting the nucleation and condensation processes occurring within the vapor jet. The in vitro MMAD of the PG aerosol changed as a function of the applied energy, suggesting that for any pharmaceutical application, the choice of applied energy is critical to deposition profile of the aerosol.

Administration, Inhalation↗

PubMed2001

A stability-indicating HPLC assay method for budesonide.

The official (European) pharmacopeial assay for budesonide was found to be non-specific and non-stability-indicating when used to qualify several batches of pharmaceutical grade drug substance from different sources. In contrast, the most widely cited HPLC method in the literature was found to be specific and stability-indicating with respect to drug substance stored in the dry state. However, that method failed the pharmacopeia's assay system suitability requirements because of peak tailing. Moreover, it was unable to detect or resolve two major degradation products which resulted from drug storage in non-aqueous solution. A new stability-indicating HPLC method described here overcomes these problems. This method used a Hypersil C18 column with a mobile phase consisting of ethanol-acetonitrile phosphate buffer (pH 3.4; 25.6 mM) (2:30:68, v/v/v), a flow rate of 1.5 ml/min and UV detection at 240 nm. The purity of budesonide EP and its impurity profile (related substances) were tested using the new assay method, and the results compared to those from the two other methods described above. Solid-state and solution stressed stability samples were used to evaluate all methods. Using the novel method, the epimers of budesonide. their related impurities and degradation products were separated successfully. Validation studies demonstrated that the novel method possessed a linear UV response, good system precision and accuracy, high sensitivity and specificity for budesonide. The novel method will be used for future studies of budesonide's degradation kinetics.

Anti-Inflammatory Agents↗

PubMed1998

Water vapor sorption studies on the physical stability of a series of spray-dried protein/sugar powders for inhalation.

One theory suggests that by maintaining the protein in an amorphous glassy sugar matrix, the physical hindrance encountered by the protein functions to stabilize it. Thus, the nature of the sugar/protein interaction is important as is the maintenance of the sugar in an amorphous form without any recrystallization. Moisture is known to function as a plasticizer and facilitate crystallization and thus loss of the amorphous state. We report the effect of cospray-drying with different proteins on the physical stability of lactose and mannitol. Particle sizing showed their suitability for inhalation, and the effect of exposure of the spray-dried products to moisture vapor was monitored gravimetrically. Bovine liver catalase, bovine pancreatic insulin, and bovine pancreatic ribonuclease A when individually cospray-dried with lactose showed no extensive initial crystallinity by powder X-ray diffraction, but proteins cospray-dried with mannitol generally showed evidence of mannitol component crystallinity. Catalase appeared to inhibit lactose crystallization from an amorphous matrix to a greater extent than insulin when exposed to short-term elevated humidity, but this difference was a kinetic feature. The hygroscopicities of the cospray-dried materials differed and indicated that each protein/sugar system required individual characterization to identify an optimal formulation.

Catalase↗

PubMed1997

Relative bioavailability of salbutamol to the lung following inhalation via a novel dry powder inhaler and a standard metered dose inhaler.

AIMS: The number of dry powder inhaler (DPI) devices could increase because they are easier to use than a metered dose inhaler (MDI). Using urinary excretion, the relative bioavailability of salbutamol to the lungs and the body for a prototype DPI has been compared with an MDI. METHODS: A randomized, double-blind, two way crossover study compared the amount of salbutamol in the urine 30 min following inhalation of 2 x 100 micrograms salbutamol from a prototype DPI (Innovata Biomed Ltd, UK) and a Ventolin (Allen and Hanburys Ltd, UK) MDI in 10 volunteers. The amount of salbutamol and its metabolite, the ester sulphate conjugate, renally excreted up to 24 h post inhalation was also determined to evaluate the relative bioavailability of salbutamol to the body. RESULTS: The mean (s.d.) 30 min post-treatment urinary excretion for the prototype DPI and MDI was 8.4 (2.6) and 5.0 (1.9) micrograms, respectively (P < 0.001). The total amount of salbutamol and its ester metabolite excreted in the urine over the 24 h period after inhalation was 187.9 (77.6) and 137.6 (40.0) micrograms (P < 0.05). CONCLUSIONS: The prototype DPI delivered more salbutamol to the body and the lungs than a conventional MDI. This finding supports further development of the prototype DPI. The urinary salbutamol method is able to discriminate between two different inhalation systems.

Administration, Inhalation↗

PubMed1995

Dry powder inhalers are bioequivalent to metered-dose inhalers. A study using a new urinary albuterol (salbutamol) assay technique.

Metered-dose inhalers (MDIs) are extensively used to deliver drugs to the lungs but are driven by chlorofluorocarbon (CFC) propellants. The worldwide phasing out of CFCs within the next 5 to 10 years presents difficulties to the pharmaceutical industry. The mean +/- SD relative lung bioavailability of albuterol to the lung following inhalation of 400 micrograms of albuterol from an MDI, the Rotahaler and Diskhaler in 10 well-trained volunteers, was 2.83 (0.78), 1.72 (0.99), and 2.64 (1.23)%, respectively, expressed as a percentage of the nominal dose. The delivery of albuterol to the lungs from the MDI and Diskhaler was similar. In nine asthmatic subjects, the relative lung bioavailability of albuterol following inhalation with the MDI and Diskhaler was 1.19 (0.79) and 2.38 (1.46)%, respectively, expressed as a percentage of the nominal dose. There was no difference in reversibility 30 min after administration of the dose by the two methods. Similar lung deposition from the Diskhaler in volunteers probably is due to efficient MDI technique, which was absent in the asthmatic subjects. The Diskhaler does not rely on coordination during inhalation and therefore is easier to use.

Adult↗

PubMed1994

Relative bioavailability of salbutamol to the lung following inhalation using metered dose inhalation methods and spacer devices.

BACKGROUND: Inhalation aids do not require coordination between actuation of a metered dose inhaler (MDI) with inspiration and reduce oropharyngeal impaction. The delivery of salbutamol to the lung and systemic availability following inhalation with three commonly used spacers and an open mouth technique have been evaluated using a simple noninvasive technique based on urinary excretion 30 minutes and 24 hours after the dose. METHODS: Ten healthy subjects inhaled, on randomised study days, 4 x 100 micrograms from a Ventolin MDI and, subsequently, with the aid of a Volumatic, Bricanyl Spacer, and Nebuhaler spacer device. In addition, an open mouth inhaler technique was evaluated. Urine samples were collected 0-30 minutes and 0.5-24 hours after inhalation. From these samples the relative bioavailability to the lung (urinary salbutamol excretion 30 minutes after dosing) and the systemic bioavailability of the dose (24 hour urinary excretion of salbutamol and its metabolite) for each inhalation method was obtained. RESULTS: The mean (SD) urinary excretion of salbutamol 30 minutes after inhalation using the MDI alone and with the Volumatic, Bricanyl Spacer, Nebuhaler, and open mouth technique was 2.83 (0.78)%, 3.37 (0.69)%, 4.09 (0.91)%, 4.34 (1.60)%, and 3.49 (0.98)%, respectively, expressed as a percentage of the nominal dose. The nebuhaler and Bricanyl Spacer spacer devices were found to increase the relative bioavailability of salbutamol to the lung compared with the MDI alone. Compared with the MDI the inhalation aid increases were much greater than the intra-individual variability of the urinary excretion method. In 11 individuals who each repeated the same inhalation procedure on four separate occasions, the mean (SD) coefficient of variation was 8.24 (2.36)%. The mean (SD) 24 hour urinary excretion of salbutamol and its metabolites was 26.6 (6.79), 27.0 (7.95), and 55.6 (9.74)% of the salbutamol dose for the Volumatic, Nebuhaler, and MDI, respectively. Similar values following the open mouth method and Bricanyl Spacer were 48.9 (10.97)% and 43.8 (11.57)%. These values, representing the systemic availability of the inhaled dose, were lower when inhaling with the aid of the Volumatic and Nebuhaler than inhalation from the MDI alone. CONCLUSIONS: Spacer devices improve pulmonary bioavailability of salbutamol and reduce the systemically available dose.

Administration, Inhalation↗

PubMed1993

Investigations of an optimal inhaler technique with the use of urinary salbutamol excretion as a measure of relative bioavailability to the lung.

BACKGROUND: A simple non-invasive method, in which a urine sample is taken 30 minutes after drug administration, has previously been shown to be a measure of the relative bioavailability of salbutamol to the lungs. This technique has been used to determine an optimal inhaler technique with commercially available metered dose inhalers (MDI). METHODS: Ten healthy subjects were trained in the use of MDIs. Each inhaled 4 x 100 micrograms salbutamol in a series of experiments to examine the relative bioavailability to the lung after different respiratory manoeuvres. Urine collection intervals were 0-0.5 hours and 0.5-24 hours after administration. RESULTS: There was significantly greater elimination of unchanged salbutamol 30 minutes after administration, indicating a greater relative bioavailability of salbutamol to the lungs after (1) exhaling gently to residual volume rather than to functional residual capacity before inhalation; (2) slow inhalation (10 l/min) compared with fast inhalation (50 l/min); (3) breath holding for 10 seconds after inhalation compared with no breath holding. CONCLUSIONS: All patient information leaflets and healthcare personnel should standardise the instructions given to patients and should adopt the inhalation method proposed.

Administration, Inhalation↗

PubMed1992

Determination of the relative bioavailability of salbutamol to the lung following inhalation.

1. The urinary excretion of salbutamol and its sulphate metabolite was measured following oral (4 mg) and inhaled (4 x 100 micrograms) administration of salbutamol. 2. Total urinary recovery of salbutamol and its sulphate conjugate indicated a mean (s.d.) relative bioavailability of 92.2 (24.8) % following inhalation compared with oral administration. 3. The mean (s.d.) elimination half-lives of salbutamol and its sulphate conjugate were 5.7 (1.4) and 4.1 (2.1) h, respectively, after oral administration and following inhalation they were 6.1 (2.1) and 5.1 (1.0) h, respectively. 4. Following oral and inhaled administration it was found that in the first 30 min the mean (s.d.) percentage of the dose excreted in the urine as unchanged salbutamol was 0.18 (0.14) and 2.06 (0.80) %, respectively (P < 0.01). The drug content of a urine sample taken 30 min after inhalation is, therefore, considered to be representative of the amount of drug delivered to the lungs. It is proposed that this method can be used to evaluate the relative bioavailability of salbutamol to the lung following inhalation by different techniques and devices.

Administration, Inhalation↗

PubMed1989

Diagnosis and treatment of asthma across Europe.

It is widely recognized that the mortality rate for asthma is at an unacceptably high level. Many physicians take the view that, if this situation is to be reversed, emphasis should be placed on the earlier and regular use of preventive therapies, which manage the fundamental pathophysiology of asthma, rather than merely treating symptoms. It, therefore, appears appropriate to reappraise sodium cromoglycate in terms of its role in normalizing respiratory function by its effect on inflammatory mediators and, thus, in improving the quality of life for asthmatics.

Adolescent↗