Powder in hard gelatin capsules

G Reier, R Cohn, S Rock, F. Wagenblast. Evaluation of factors affecting the encapsulation of powders in hard gelatin capsules I. Semi-automatic capsule machines. J Pharm Sci 57 660-666, 1968. 

During early preformulation studies, capsule formulations are used in Lrst clinical trials. Initially, only a low amount of active substance is used forthe Lrst clinical trials. Subsequently, the dose may be increased to Lnd the optimal therapeutic effect with a minimum of side effects. For this purpose, the amount of drug substance is increased and the amount of Lller, usually lactose, is decreased in the powder mixture that is Llled in hard gelatin capsules (von Orelli and Leuenberger, 2004, ongoing research). 

York, P. Analysis of moisture sorption hysteresis in hard gelatin capsules, maize starch, and maize starch drug powder mixtures. J. Pharm. Sci. 1981, 33, 269-273. 

The manufacture of tablets, and to a lesser extent powder-filled hard gelatin capsules, involves the process of powder compaction, the purpose of which is to convert a loose incoherent mass of powder into a single solid object. Knowledge of the behaviour of powders under pressure, and the way in which bonds are formed between particles, is essential for the rational design of formulations. 

Hard gelatin capsules are uniquely suitable for blinded clinical tests and are widely used in preliminary drug studies. Bioequivalence studies of tablet formulations may be conveniently blinded by inserting tablets into opaque capsules, often along with an inert filler powder. Even capsule products may be disguised by inserting them into larger capsules. 

This section addresses the design of immediate-re-lease powder formulations for hard gelatin capsules. In general, powder formulations for encapsulation should be developed in consideration of the particular filling principle involved. The requirements imposed on the formulation by the filling process, such as lubricity, compressibility and/or compactibility, and fluidity can vary between machine types. Furthermore, the... 

Another approach to improving the wettability of poorly soluble drugs is to treat the drug with a solution of a hydrophilic polymer. Lerk et al. [137] reported that both wettability of the powder and the rate of dissolution of hexobarbital from hard gelatin capsules could be greatly enhanced if the drug were treated with methylcellulose or hydroxyethylcellulose. In this process, called hydrophilization, a solution of the... 

Laminar flow conditions are typically used for tablets, hard gelatin capsules, powders, and granules. Suppositories and soft gelatin capsules are placed in the cell without beads for turbulent flow. Nicolaides, Hempenstall, and Reppas have reported differences in the dissolution rate of a poorly soluble drug, tiaglitazone, from an immediate-release (IR) tablet formulation based on the presence or absence of a tablet holder and/or beads in the flow-through cell. 

The primary function of tablet lubricants is to reduce the friction arising at the interface of tablet and die walls during compression and ejection. Lubricants also possess antiadherent (prevention of sticking to the punch and, to a lesser extent, to the die wall) and gli-dant (improvement of flow characteristics of powders or granulates) characteristics and are useful in the processing of hard gelatin capsules. 

Powdered cellulose is used as a tablet diluent and a hard gelatin capsule filler see Table I. In both contexts it acts as a bulking agent to increase the physical size of the dosage form for formulations containing a small amount of active substance. 

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