N. Anthony Armstrong

The influence of viscosity on the migration of chloramphenicol and 4-hydroxybenzoic acid through glycerogelatin gels.

Migration of chloramphenicol and 4‐hydroxybenzoic acid from solutions in 1‐octanol into Glycerol Suppository Base, BP and soft gelatin capsule shells is reported. Rates of migration through the gels, quantified in terms of diffusion coefficients, are given. An electron spin resonance probing technique was used to determine the microscopic viscosity. The latter, rather than the bulk viscosity, was shown to be the major rheological influence on the rate of diffusion.

Studies on Powder Plug Formation Using a Simulated Capsule Filling Machine

Using an apparatus which simulates the action of a Macofar 13‐2 dosating‐type capsule‐filling machine, the variation in plug weight and density with changing machine parameters has been studied.

The effect of film composition on the diffusion of ethanol through soft gelatin films

Abstract Changes were made in the composition of plasticized gelatin gels, analogous to those used in the manufacture of soft shell capsules, and the effect of these changes on the diffusion of ethanol through the films was investigated. The substitution of glycerol by higher polyols such as xylitol, sorbitol and lycasin (hydrogenated corn syrup) caused a significant reduction in the diffusion process, as indicated by a reduction in the apparent diffusion co-efficient. When allowance was made for film moisture content, a 5–10-fold reduction in the apparent diffusion co-efficient was observed with the greatest reduction occurring in films having lower moisture contents. This reduction in apparent diffusion co-efficient is believed to be due to a ‘phobic’ interaction between ethanol and the higher polyols which increases the energy barrier to the diffusion process. A general case is postulated whereby any diffusion process will be modified by the inclusion of ‘diffusantophilic’ (increased rate of diffusion) or ‘diffusantophobic’ (reduced rate of diffusion) components in the barrier. The implications of the changes in the formulation of the films for the filling of soft shell capsules by the rotary-die method is discussed. Attempts to modify diffusion by inclusion of solid particles or liquid crystals in the gel structure were unsuccessful, as was the replacement of part of the gelatin by hydrolyzed gelatin.

The effect of gelatin grade and concentration on the migration of solutes into and through glycerogelatin gels.

Abstract— The diffusion of 4‐hydroxybenzoic acid and phenobarbitone through glycerogelatin gels was found to be independent of the type of gelatin used. Three types of gelatin, two acid‐processed and one alkali‐processed were studied, and the bulk viscosities of gels prepared from them was seen to vary considerably. However, the microviscosities of the gels, as measured by ESR, showed no significant differences. Thus microviscosity was the factor governing diffusion. Gelatin concentration in aqueous solutions without glycerol influenced microviscosity and hence diffusion. This is believed to be caused by dissolution of water‐soluble fractions of the gelatin. Interstices in the gelatin matrix, though reduced in size when gelatin concentration is raised, are still too large to act as physical barriers to diffusing molecules. It is suggested that hydrated gelatin forms the matrix of glycerogelatin mixtures and that the interstitial fluid, through which migration occurs, consists almost entirely of glycerol and water.

Construction of an Intermittent-Motion Capsule Filling Machine Simulator

A pneumatically operated apparatus is described which simulates the forces generated by and the component movements encountered in a Macofar 13/2 dosator type capsule filling machine. Force transducers are fitted to the dosing piston and dosator tip, and the movement of the dosator piston and the powder bed followed by displacement transducers. Calibration of the transducers is described. The output from the transducers is collated, stored and manipulated by microcomputer. The manufacturing parameters which can be studied using this apparatus are discussed.

An apparatus for investigating drug migration into gelatin capsule shells

Abstract An apparatus for the study of migration of a solute from its solution in a non-aqueous solvent into the walls of soft shell capsules is described. The solution is applied to the top of a glycerogelatin column contained in a truncated hypodermic syringe. After the required period of time, the column is extruded from the syringe, cut into slices, and each slice analysed. The reproducibility of the method was established by following the migration of 4-hydroxybenzoic acid from isopropyl myristate solution into glycerol suppository base, and the technique extended to soft and hard gelatin capsule bases. The influence of temperature indicated that Arrhenius type plots could be used for accelerated testing, and migration from 1-octanol, isopropyl myristate and blends of the two showed that the rate and extent of migration were dependent upon the partition coefficient.

Relationship between porosity and water content of dicalcium phosphate tablets

Abstract The effect of water content on the consolidation of dicalcium phosphate dihydrate (Emcompress) tablets was examined. Increasing the moisture content of Emcompress resulted in an increase in apparent tablet density, both under compression and after ejection. This continued up to a critical water content, beyond which a reduction in densification was obtained. The magnitude of this critical water content was dependent on the applied compression force, in that it was decreased by an increase in compression force. Increasing the moisture content also caused a reduction in elastic decompression work and yield force values to a minimum, beyond which an increase in the values of both parameters was recorded.

Design and use of an apparatus for measuring diffusion through glycerogelatin films

Abstract The diffusion of ethanol into and through soft gelatin films analogous to capsule shell formulations during the drying process has been investigated using a specially designed diffusion cell. Using microcomputer-controlled sampling, it was possible to monitor the diffusion through films at regular intervals for periods of 24 h and longer. Films having moisture contents in the range 4.5–42% w/w were investigated. The moisture content of the glycerogelatin soft gelatin capsule shell formulations has an important influence on the diffusion process; the higher the moisture content, the more rapid the diffusion of ethanol.

An in vitro model to simulate drug release from oily media

Abstract An in vitro method of measuring the release of drugs from non-polar media is described. The technique is based on the Sartorius Absorption Simulator. The base is spread as a thin film on a base plate, and the drug must diffuse across an aqueous layer before transfer through a simulated biomembrane. Salicylic acid was used as a model drug. The reproducibility of the technique is assessed, and 3 methods are given for manipulation of the release data; that for opposing first-order reactions was found to be the most appropriate. The fraction of drug released is shown to be dependent on the amount of base applied. It is suggested that the technique may be applicable to topical and rectal dosage forms and eye ointments.

A Comparative Study of the use of Enset and Potato Starches in Tablet Formulations

AbstractEnset and potato starches have been compared as binding agents and disintegrants in tablets made with paracetamol and chloroquine phosphate. Tablet crushing strengths, friabilities and disintegration times have been measured. The results show that enset starch can be used both as a binding agent and disintegrant. It has a better binding ability than potato starch, giving tablets of lower porosity. However because of this, tablets containing enset starch disintegrate more slowly.