C.G. Wilson

The effect of different oils on the absorption of probucol in the rat

The effect of oily vehicles on the gastrointestinal absorption of the hypocholesterolaemic agent probucol has been investigated in the rat. The plasma concentration was determined following its administration in arachis oil (peanut oil), Miglyol 812 (fractionated coconut oil) and liquid paraffin. The total absorption of the drug, calculated as the area under the plasma concentration time curve, was significantly greater for the arachis oil formulation than with the other vehicles. The drug was selectively absorbed via the lymphatic system, lymph drug concentrations being highest following co‐administration of arachis oil.

The influence of solution viscosity on nasal spray deposition and clearance

Abstract Three hydroxypropyl methylcellulose solutions, having kinematic viscosities 36, 120 and 430 mm 2 ·s −1 , were administered as nasal sprays to 8 healthy subjects. The solutions were radiolabelled with 99m Tc-labelled diethylenetriaminepentaacetic acid and the sites of deposition and the rates of clearance from the nasal cavity monitored using a gamma camera. The areas of deposition were the same for all the solutions. The clearance rates decreased with increasing solution viscosity, the half-times being 1.0, 1.7 and 2.2 h. Thus increasing the solution viscosity may provide a means of prolonging the therapeutic effect of nasal spray preparations.

Bimodal release of ibuprofen in a sustained-release formulation: a scintigraphic and pharmacokinetic open study in healthy volunteers under different conditions of food intake

Abstract The position of a radiolabelled sustained release ibuprofen formulation containing 800 mg drug and labelled by the addition of 10 mg [ 111 In] ion-exchange resin has been followed by gamma scintigraphy in 11 healthy male and female volunteers. The study was conducted first in 5 volunteers who received the tablet with a light breakfast and then as a cross-over study in a separate group of 6 volunteers who had either fasted or ingested a heavy breakfast. Mean times ( ± S.D.) for gastric emptying of the unit were 1.0 ± 0.4 h (fasted, n = 6), 2.0 ± 0.9 h (light breakfast, n = 5) and 8.8 ± 5.9 h (heavy breakfast, n = 4). There were no significant was observed to remain intact until it reached the ascending and transverse colon where it broke into two or three pieces or completely disintegrated. In two subjects, in which the tablet had been administered with a heavy meal, the unit remained in the stomach for more than 15 h. The presence of food markedly altered the pharmacokinetics of the drug which, in fasting subjects, was characterised by a double peak in the plasma concentration time profile. The light breakfast caused a levelling of the two peaks to a plateau lasting from 4 to 13 hours, whereas after the heavy breakfast only the secondary peak was evident. The secondary peak appears to be due to a disintegration of the matrix after 12–14 h coupled with a high absorptive capacity for the drug in the ascending colon. There was no evidence of adhesion of the unit to the gastrointestinal mucosa.

The transit rate of different-sized model dosage forms through the human colon and the effects of a lactulose-induced catharsis

Gamma scintigraphy has been used to compare the colonic transit rate of different sizes of radiolabelled model dosage forms in healthy human subjects. Studies simultaneously compared the ascending colon residence time of 111In-labelled 0.2 mm ion-exchange resin particles and 99mTc-labelled 5 or 8.4 mm non-disintegrating tablets. Under normal conditions, no difference was observed between the rate of transit through the ascending colon of 0.2 mm particlesvs 5 mm tablets (n = 11) or 0.2 mm particles vs 8.4 mm tablets (n = 10). The mean period of residence of 50% of the administered 0.2 mm particles in the ascending colon was 11.0 ± 4.0 h (n = 21). Coadministration of the laxative, lactulose, to subjects receiving the 0.2 and 5 mm particles significantly accelerated colonic transit. Under these conditions, the ascending colon residence of the 0.2 mm resin was significantly shorter than for the 5 mm tablets, although the magnitude of the effect was small.

The behaviour of a fast-dissolving dosage form (Expidet) followed by γ-scintigraphy

Abstract The residence time in the mouth and the distribution of a fast-dissolving dosage form have been followed by γ-scintigraphy in a group of healthy young adults. This was facilitated by incorporation of micronised radiolabelled ion exchange resin (10 mg) into the formulation. Reduction of the amount of resin to 2.5 mg decreased the rate of clearance due to trapping in the macrostructure (papillae) of the tongue. Incorporation of salivary stimulants into the formulation did not alter the rate of dissolution of the dosage form. Measurements of the release rate of oxazepam or lorazepam from the formulation whilst it was in the buccal cavity indicates that little drug absorption occurs from the superior surface of the tongue over short time periods.

The in‐vivo evaluation of an osmotic device (Osmet) using gamma scintigraphy

The release of a radiolabelled marker from an orally administered osmotic pump device (Osmet) has been evaluated in‐vivo in a group of 6 subjects, using the technique of gamma scintigraphy. The duration of residence of the pump in the stomach was greatly influenced by food intake. However, the release of the marker from the device was independent of food and position within the gastrointestinal tract. Furthermore, the material released from the osmotic pump was well distributed in the gastrointestinal tract. Good agreement between in‐vitro and in‐vivo release rates was obtained.

The influence of food on the gastric emptying of multiparticulate dosage forms

Abstract Gastric emptying of multiparticulate systems has been monitored in healthy volunteers. Particles dosed before a meal emptied exponentially, whilst those taken along with and after a meal exhibited a linear pattern of emptying. Although dosing before eating resulted in an initially faster emptying rate, the overall half-times of about 3–4 h were similar for all the dosing regimens. Particles dosed predispersed with the food emptied from the stomach at the same rate as those taken in a capsule.

Scintigraphic assessment of the in vivo dissolution rate of a sustained release tablet

Abstract The release of [ 99m Tc]diethylenetriaminepentaacetic acid ([ 99m Tc]DTPA) from a matrix tablet formulation was measured by external scintigraphy in 4 healthy male volunteers. The rate determined was compared with that observed in vitro using a U.S.P. dissolution apparatus. The in vitro release rate of [ 99m Tc]DTPA was similar to that of chlorpheniramine, and therefore the labelled compound was used to model the release of this drug in vivo. The in vitro release of [ 99m Tc]DTPA was pH-independent.

Pharmacokinetics and in vivo scintigraphic monitoring of a sustained release acetylsalicylic acid formulation

Abstract The in vivo dissolution and pharmacokinetics of a sustained release aspirin formulation labelled with ( 99m Tc]diethylenetriaminepentaacetic acid has been monitored in 5 subjects by the use of gamma scintigraphy and drug analysis undertaken of blood and urine samples. The data obtained enabled the position of the tablet in vivo to be related to the plasma and urinary salicylate levels. The study confirms the sustained release properties of the cellulose acetate phthalate formulation.

Assessment of Disintegration and Dissolution of Dosage Forms In Vivo Using Gamma Scintigraphy

AbstractThe measurements of the in vitro rate of disintegration and dissolution of dosage forms are considered to be the most available predictors of the behaviour of dosage forms and the plasma concentration - time profile. However, the interaction of the formulation with physiological processes has shown that prediction of bioavailability by such simple tests is inadequate and has highlighted the need to establish methodology which would enable the determination of in vivo rates of dissolution and disintegration. Over the past ten years, the technique of gamma scintigraphy has made a significant contribution to the understanding of the behaviour of formulations in the body. This review provides an overview of the technique and its advantages and limitations in pharmaceutical research, together with illustrations showing some of the applications in the measurement of disintegration and dissolution of dosage forms.