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Development of a potentially wearable glucose sensor for patients with diabetes mellitus: design and in-vitro evaluation

A potentially wearable glucose sensor was developed, consisting of an oxygen electrode as detector and a dynamic enzyme perfusion system as selector. The selector is a hollow fibre, which can be placed subcutaneously and dialyses glucose from tissue fluid. In this design the problems of enzyme instability and oxygen limitation might be circumvented. The sensor measures glucose reliably for over two weeks, provided a new 10 ml syringe containing a glucose oxidase solution is connected to the system each day.

EVALUATION OF ANHYDROUS ALPHA-LACTOSE, A NEW EXCIPIENT IN DIRECT COMPRESSION

AbstractDifferent forms of lactose are available for direct compression of tablets. The use of spray-dried lactose, which has good flow and compressibility characteristics, is limited by its stability when stored under humid conditions. Sieved crystalline fractions of α-lactose monohydrate such as the 100 mesh fraction, have very good flow properties and an outstanding stability, but the compressibility is so poor, that it can be used only in combination with other filler-binders, like microcrystalline cellulose. A third form of lactose, increasingly used in direct compression is anhydrous lactose. The commercially available products generally consist of an excess of β next to α-lactose. They both have good binding and stability characteristics, but a flowability which is less than optimum. The latter is caused by the rather irregular particle shape and the relatively high amount of fines. A newly developed form of lactose is anhydrous α-lactose. It is prepared by dehydration of α-lactose monohydrate. Bin...

NATIVE STARCH IN TABLET FORMULATIONS - PROPERTIES ON COMPACTION

Maize, potato, rice and tapioca (cassava) starch were evaluated with respect to their properties on direct compression. Rice starch showed much better compactibility as compared to maize, potato and tapioca starch. Moreover, its binding capacity proved to be almost insensitive to mixing with magnesium stearate. This in contrast to the dramatic decrease in crushing strength of potato starch tablets containing the lubricant. The compactibility of the starches was found to be strongly affected by the equilibrium moisture content of the starches, which is dependent on the relative humidity of the atmosphere under which the powders were stored. All starches showed adequate capacity for water uptake to act as a disintegrant. Rice starch exhibited worst flowability, caused by its fine particle size as compared to the other starches. Granulation of rice starch changed it into a potential filler-binder in tablets prepared by direct compression.

ORAL CONTROLLED RELEASE DOSAGE FORMS - A REVIEW

When a drug meets the criteria which make incorporation into a controlled release dosage form rational, a proper dosage form has to be selected. Oral controlled release products, available on the Dutch market, are referred to in discussing the various methods used to control drug release by galenical means in order to achieve a prolonged therapeutic effect. The effects of some physiological variables of the alimentary tract on drug delivery from the various dosage forms, especially with regard to formulation and design, are reviewed.

FORMATION AND ANTIMICROBIAL ACTIVITY OF COMPLEXES OF BETA-CYCLODEXTRIN AND SOME ANTIMYCOTIC IMIDAZOLE DERIVATIVES

Complex formation between β-cyclodextrin and six antimycotic imidazole derivatives has been studied. The solubility of all drugs was increased in the presence of β-cyclodextrin. The smallest increase (approx. 5-fold) was observed for miconazol, and the largest increase (approx. 160-fold) was observed for bifonazol. Apparent I:I-complex constants were measured and found to decrease in the order: bifonazol > ketoconazol > tioconazol > miconazol > itraconazol > clotrimazol. The complexes appeared to possess a low, if any, antimicrobial activity. Measurement of inhibition zone sizes, with four test organisms was used to study the release of the antimycotic drugs from topical preparations. The antimycotic drugs were more readily released from topical preparations containing \-cyclodextrin than from the same vehicles without β-cyclodextrin. The rationale of β-cyclodextrin addition to antimycotic topical preparations is discussed.

DEVELOPMENT AND OPTIMIZATION OF PHARMACEUTICAL FORMULATIONS USING A SIMPLEX LATTICE DESIGN

The composition of pharmaceutical formulations is often subject to trial and error. This approach is time consuming and unreliable in finding the best formulation. Optimization by means of an experimental design might be helpful in shortening experimenting time. Such a design with the concomitant mathematical models, reveals effects and interactions of the variables. The independent variables are the different compositions of the mixtures of the chosen ingredients [drug(s) and excipients]. The dependent variables are the properties (responses) of the formulation. When all responses of interest have been expressed in models that describe the response as a function of the composition of the mixture, the models can be combined graphically or mathematically to find a composition satisfying all demands. In this paper an introduction to the use of mixture designs will be given by means of a theoretical part and an example: optimizing a tablet formulation consisting of excipients only.

The Effect of Magnesium Stearate Admixing in Different Types of Laboratory and Industrial Mixers on Tablet Crushing Strength

AbstractIt is generally known that hydrophobic lubricants such as magnesium stearate can have a strong negative effect on the binding properties of directly compressible filler-binders. It was found that the decrease in binding forces is not only dependent on the tablet ingredients and the lubricant concentration used, but especially on the mixing time and mixing procedure. Most studies were performed, however with small laboratory scale mixers. In order to evaluate the effect of magnesium stearate admixing in different types of laboratory-scale and industrial mixers, the decrease in crushing strength was measured for a test formulation during mixing with the lubricant in different mixers. The formula used consisted of 90% a-lactose monohydrate 100 mesh, 9.5% microcrystalline cellulose and 0.5% magnesium stearate. The mixers used were two laboratory scale mixers: a 2 litre Turbula mixer and a 13 litre cubic mixer and five production scale mixers: a 45 litre drum mixer, 90 litre, 200 litre and 900 litre pl...

On the Similarity of Sodium Starch Glycolate from Different Sources

AbstractThe physico-pharmaceutical properties of different batches of two brands of sodium starch glycolate have been investigated as disintegrant in direct compression. Differences in disintegration efficiency were found to be related to the purity of the products. The differences, however, were too small to have practical significance. The currently available low-sodium chloride content sodium starch glycolates may consequently be considered as being pharmaceutically equivalent, when used as disintegrant in tablet formulations.

IMPROVEMENT BY SUPER DISINTEGRANTS OF THE PROPERTIES OF TABLETS CONTAINING LACTOSE, PREPARED BY WET GRANULATION

The crushing strength, disintegration and dissolution properties of tablets, made by wet granulation with lactose as filler, gelatin as binder, potato starch as disintegrant and magnesium stearate as lubricant can be markedly improved when the potato starch (20%) is replaced by a much lower concentration (4%) of an insoluble super disintegrant, such as sodium starch glycolate (Primojel®) or crospovidone (Polyplasdone®Xl). The incorporation of partially water soluble super disintegrants such as low-substituted sodium carboxymethylcellulose (Nymcel®,Zsd 16), causing a viscous barrier in the tablets when containing water, is shown to be deleterious for both tablet disintegration and drug release.In contrast to potato starch, the position of the super disintegrants (intragranular, extragranular or equally distributed) had hardly any effect on the tablet properties. The improved properties of the tablets containing insoluble super disintegrants, when compared to tablets with potato starch, are the result of the use of a much lower concentration of disintegrant, but especially of the difference in effect of magnesium stearate on the disintegration capacity of the slightly swelling potato starch and the strongly swelling super disintegrants, respectively. The latter cause, even in the presence of the liquid penetration inhibiting hydrophobic magnesium stearate, a chain reaction of opening of the tablet, starting at the outside and resulting in a fast disintegration.

The effect of the swelling capacity of disintegrants on the in vitro and in vivo availability of diazepam tablets, containing magnesium stearate as a lubricant

Abstract The disintegration and dissolution rate of diazepam tablets, containing the slightly swelling disintegrant, potato starch, depend on mixing time of the drug/excipient preblend with the lubricant magnesium stearate. During the mixing process, a hydrophobic lubricant film is formed on the excipient particles, which decreases the penetration of water into the tablet, and as a result, increases the disintegration time. On the other hand, disintegration and drug dissolution rate of tablets with the strongly swelling disintegrant sodium starch glycolate, are hardly affected by mixing with magnesium stearate. The difference in effect of the lubricant on the disintegrants is explained by the difference in swelling capacity of the disintegrants. The dissolution rate of tablets with potato starch strongly depends on both the dissolution model (i.e. USP XX basket-model and paddle-model) and stirring rate (i.e. 50 or 100 rpm.). For tablets with the strongly swelling sodium starch glycolate the dissolution rate is less affected by the dissolution method. The discrimination between the tablets is best using a method with mild hydrodynamic conditions. The bioavailability of diazepam from these tablets was studied in human volunteers. Significant differences in absorption parameters were found. However, the influence of the swelling capacity of the disintegrant and the mixing time on absorption rate is less pronounced than was expected from the in vitro dissolution tests. A correlation of in vitro dissolution and in vivo absorption has been found for the model with a relatively high stirring rate, which is less discriminating in vitro.