Jm Newton

The tensile strength of lactose tablets.

animals that received the monoamine oxidase inhibitor and the a-methyltyrosinecontaining diet, motor activity and brain amine levels were lower than corresponding control values. However, values for the spontaneous locomotor activity and the brain content of noradrenaline were significantly higher in the pheniprazine-a-methyltyrosine group than in saline-cr-methyltyrosine group. Although pheniprazine partially blocked the behavioural depression and noradrenaline depletion it did not alter plasma levels of a-methyltyrosine. Thus the behavioural depression after a 24 hr diet containing a-methytyrosine appears to be related to the brain levels of catecholamines. This work was supported by USPHS Grant AM-1 1083. L-a-Methyltyrosine was kindly supplied by Dr. C. A. Stone, Merck Institute for Therapeutic Research, West Point, Pa., U.S.A. Pheniprazine (JB-5 16, Catron) was supplied by Dr. R. C. Ursillo, Lakeside Laboratories, Milwaukee, Wisconsin, U S A . The technical assistance of Mrs. M. Grarnatins and Mrs. D. Simpson is gratefully acknowledged.

Amylose as a coating for drug delivery to the colon: Preparation and in vitro evaluation using 5-aminosalicylic acid pellets

Abstract Colon-specific drug delivery may be possible by the application of dried amylose films to pharmaceutical formulations. Amylose, one of the major fractions of starch, possesses the ability to form films through gelation, when prepared under appropriate conditions. The microstructure of the film is potentially resistant to the action of pancreatic a-amylase but is digested by amylases of the colonic microflora. However, under simulated gastro-intestinal conditions, coatings made solely of amylose swell, become porous and allow drug release. Incorporation of insoluble polymers into the amylose film, to control amylose swelling, provides a solution to this problem. A range of cellulose and acrylate based copolymers were assessed, of which a commercially available ethylcellulose (Ethocel®) was found to control the swelling most effectively. The in vitro dissolution of various coated pellets under simulated gastric and small intestinal conditions, using commercially available pepsin and pancreatin, was determined and demonstrated the resistance of the amylose-Ethocel® coat ( 1:4 w/w ) to such conditions over a period of 12 h. With additional thermal treatment of the coat, in vitro drug release under simulated gastric and small intestinal conditions was prevented further, even after storage of the product for one year. Coated pellets were further evaluated in a batch culture fermenter, simulating colon conditions, containing an inoculum of mixed faecal bacteria. The in vitro release of 5-aminosalicylic acid from coated pellets in the fermenter system was shown to occur.

Trends in national incidence, lifetime prevalence and adrenaline prescribing for anaphylaxis in England

Summary Background Analysis of primary healthcare datasets offers the possibility to increase understanding of the epidemiology of acute uncommon conditions such as anaphylaxis, but these datasets remain under-exploited. Aim To investigate recent trends in the recorded incidence, lifetime prevalence and prescribing of adrenaline for anaphylaxis in England. Methods QRESEARCH is one of the worlds largest national aggregated health databases containing the records of over nine million patients. We extracted data on all patients with a recorded diagnosis of anaphylaxis and calculated annual age-sex standardized incidence and lifetime period prevalence rates for each year from 2001–2005. We also analysed trends in adrenaline prescribing in those with a recorded diagnosis of anaphylaxis. National population figures were used to estimate numbers of people in England that have experienced anaphylaxis at some point in their lives. Results The age-sex standardized incidence of anaphylaxis was 6.7 per 100,000 person-years in 2001 and increased by 19% to 7.9 in 2005. Lifetime age-sex standardized prevalence of a recorded diagnosis of anaphylaxis was 50.0 per 100,000 in 2001 and increased by 51% to 75.5 in 2005. Prescribing of adrenaline increased by 97% over this period. By the end of 2005 there were an estimated 37,800 people that had experienced anaphylaxis at some point in their lives. Conclusions Recorded incidence, lifetime prevalence and prescribing of adrenaline for anaphylaxis all showed substantial increases in recent years. An estimated 1 in 1,333 of the English population have at some point in their lives experienced anaphylaxis.

Thermal studies on the interaction of water and microcrystalline cellulose.

Abstract— The interaction between water and microcrystalline cellulose in the absence and presence of lactose has been studied by thermogravimetric analysis, differential thermal analysis and immersional calorimetry. The results indicate that most of the water held within a system used for the preparation of spherical granules by extrusion/spheronization is present as free water which may be readily lost by evaporation. There is approximately 0.856 mol of water per 100 g of microcrystalline cellulose which appears to be absorbed as structured water. Microcrystalline cellulose may therefore be described as a ‘molecular sponge’. The enthalpy of fusion of the ‘free’ water offers a simple method of estimating the effective surface area of the microcrystalline cellulose.

Production of spray dried salbutamol sulphate for use in dry powder aerosol formulation

Salbutamol sulphate particles, for use in dry powder aerosol formulation, were prepared by spray drying, using a Buchi 190 mini spray dryer. The spray drying parameters were investigated in relation to particle size and yield of the resultant powder. Important factors were determined using a 24 factorial statistical design. The four factors investigated were pump speed, aspirator level (the rate at which the drying air is pulled through the dryer), inlet temperature and the concentration of the aqueous salbutamol sulphate solution dried. Spray drying conditions were chosen based on results from the experimental design and working knowledge of the spray dryer, to produce a batch of salbutamol sulphate powder on which further studies were performed. The physicochemical properties of spray dried salbutamol sulphate were compared to those of the micronised drug. Infrared spectroscopy, X-ray diffraction, appearance, particle size analysis (including aerodynamic diameter) and powder flow were investigated. It was found that spray drying produced spherically shaped particles of salbutamol sulphate having a mass median diameter of 4.5 μm (laser diffraction), mean Ferets diameter (image analysis) of 1.58 μm and a mass median aerodynamic diameter of 9.7 μm (cascade impaction), i.e., particles sufficiently small in diameter for use in inhalation formulation. The spray dried material was seen to perform as well as the micronised material in most cases with the exception of powder flow properties, where performance was slightly poorer.

Comparative gastrointestinal transit of pellet systems of varying density

Abstract Model placebo multiple unit oral dosage forms were prepared by the processes of extrusion and spheronisation. The non-invasive technique of gamma scintigraphy was used to monitor the gastrointestinal transit of these radiolabelled dosage forms. Standard sized units (1.18–1.40 mm) of density 2.0 and 2.4 g cm−3 were compared with similarly sized control units of 1.5 g cm−3. Each density was tested separately in eight healthy fasted male subjects. The results showed no differences in the gastrointestinal transit of the three formulations as measured by each of several parameters selected to describe the process. However, the results did reveal some interesting features of the gastric emptying process, and provide further information regarding the critical density at which a prolongation of gastric emptying occurs.

Gastrointestinal transit of pellets of differing size and density

The gastrointestinal transit of four multiple unit pellet dosage forms of two sizes 0.5 and 4.75 mm and two densities 1.5 and 2.6 g cm-3 was examined by gamma scintigraphy in eight healthy fasted subjects. The pellets were prepared by the processes of extrusion and spheronisation and radiolabelled with 99mTc or IIIIn. Small pellets of normal and high density were examined on one occasion and large pellets of normal and high density on another. The small and large pellet data from each administration were analysed separately, and then pooled to determine the overall effects of size and density on gastrointestinal transit. A distinct lag phase before gastric emptying commenced was observed for all pellets. The onset of emptying was not affected by size or density. Thereafter gastrointestinal transit did appear to be prolonged with an increase in density. This effect was more clearly demonstrated by the smaller pellets. Small pellet data and the pooled data indicated that an increase in density delayed gastric emptying and prolonged small intestinal residence time (p < 0.05). The large pellet data alone, also indicated that the increase in density caused a delay in gastric emptying (p < 0.05) but the prolongation of small intestinal residence time was not significant. Gastric emptying of the pellets was not affected by their size, although small intestinal residence time was prolonged by the large pellets (p < 0.05). These results and those previously reported by the authors (Clarke et al., Int. J. Pharm., (1993 in press) suggest that there may be a threshold density, of the order of 2.4-2.6 g cm-3, above which gastric emptying is prolonged. The delayed gastric emptying and prolonged small intestinal residence time have important implications for the rational design of sustained release oral dosage forms.

The influence of density on the gastrointestinal transit of pellets

Abstract— The gastric emptying, intestinal transit and caecum arrival times of 1 mm pellets of density 1.5 and 2.8 g cm−3 have been assessed in fed and fasted volunteers by means of gamma‐scintigraphy. The pellets were prepared by extrusion/spheronisation, coated with ethylcellulose and labelled with technetium‐99m. The position of the pellets in the gastro‐intestinal tract was followed by a double‐headed gamma camera to allow detailed information over a period of up to 10 h. Analysis of variance established that there was a highly significant difference in the time for 50% of the pellets to empty from the stomach both in fed and fasted states. The 2.8 g cm−3 pellets had an extended resident time in both the fed and fasted states. The gastric emptying time was prolonged in the fed state. There was no significant difference in intestinal transit time between the two formulations nor whether the volunteers were fed or fasted. The caecum arrival time was therefore modified only by the gastric emptying time.

Amylose as a coating for drug delivery to the colon: Preparation and in vitro evaluation using glucose pellets

Abstract The potential of amylose a constituent of starch, as a novel colonic drug delivery system has been investigated. In this study glucose was used as a model drug and incorporated into pellets (diameter 1.40–1.70 mm) that were prepared by extrusion and spheronisation. The behaviour of different glucose containing pellets coated with an amylose-Ethocel® mixture (ratio 1:4 w/ w) has been investigated in vitro. Dissolution release profiles of the formulation demonstrated in vitro gastric and small intestine resistance. High volatile fatty acid and carbon dioxide concentrations during in vitro fermentation studies showed that the formulation was susceptible to bacterial enzymatic attack.

A shape factor to characterize the quality of spheroids

Abstract— A shape factor eR has been devised to describe how the form of spherical particles approaches that of a true spheroid, based on a two‐dimensional image analysis. Both the deviation of shape from a circle towards an ellipse and surface irregularities influence the value of eR. Using a set of model figures such as squares, triangles, diamonds and stars, it could be shown that eR clearly differentiates between different polygonally symmetric figures, even in the case where common shape descriptors such as the aspect ratio provide equal values. The value of eR is 1·0 in the case of a perfect spheroid, while ellipticity and surface roughness lead to a significant change in the value.