INTRODUCTION

In recent years, interest in using hard gelatin capsules in developing and manufacturing medicines has increased considerably. This is most probably due to rapid advances in dosage forms for hard gelatin capsules. In tandem with this, the structural foundation of a new technology has been developed, and realized in the form of efficient process machinery. The formulation of a rapid-release hard gelatin capsule can be largely deduced from the physicochemical properties of the drug active. Usually, only a limited number of excipients are necessary, and these are simply mixed with the active and directly filled into the capsules. The costly process of granulation and compression can mostly be avoided. The choice available in terms of capsule type, the range of sizes and the capsule's colour or combination of colours, as well as the possibility of printing directly onto the capsule.

Capsules are

solid

dosage forms in which the drug

substance

is

enclosed within either a hard or soft soluble shell. The shells generally are formed from gela-t i n . T h e c a p s u l e m a y b e r e g a r d e d a s a c o n t a i n e r ' ' drug-delivery

system that provides a tasteless or odorless dosage form without the need for a secondary coating step, as may be required for tablets. Swallowing is easy f o r most

p a t i e n t s , s i n c e t h e s h e l l i s s m o o t h a n d h yd r a t e s i n t h e m o u t h , a n d t h e c a p s u l e o f t e n t e n d s t o oat upon swallowing in the liquid taken with it. Their availability in a wide variety of colors makes capsules aestheti cally pleasing.

There are numerous additional advantages to capsules as a dosage form, depending on the type of capsule employed. It m a yb e c l a s s i f e d a s e i t h e r h a r d o r s o f t depending on the nature of the shell. Soft gelatin capsules (sometimes

referred to as ``soft gels'') are made from a more flexible, plasticized gelatin film than hard gelatin capsules. Most capsules of either type are int e n d e d t o b e s w a l l o w e d .

The bulk density of a solid is often very difficult to measure since t h e s l i g h t e s t d i s t u r b a n c e o f t h e b e d m a y r e s u l t i n a n e w b u l k d e n s i t y. Moreover, it is clear that the bulking properties of a powder are

d e p e n d e n t o n t h e h i s t o r y o f t h e p o w d e r a n d i t c a n b e p a c k e d t o h a v e a range of bulk densities. Thus, it is essential in reporting bulk density to specify how the determination was made. The bulk density often is the bulk density of the powder as poured or as passively filled into a measuring vessel. The tapped density is a limiting density attained after tapping down, usually in a device that lifts and drops a volumetric m e a s u r i n g c yl i n d e r c o n t a i n i n g t h e p o w d e r a f i x e d d i s t a n c e .

Tapped density is achieved by mechanically tapping a measuring c yl i n d e r c o n t a i n i n g p o w d e r s a m p l e . A f t e r o b s e r v i n g t h e i n i t i a l v o l u m e , t h e c yl i n d e r w i l l b e m e c h a n i c a l l y t a p p e d a n d t h e v o l u m e r e a d i n g s a r e taken until little further volume change is observed. The mechanical tapping is achieved by raising the cylinder and allowing it to drop under its own weight using a suitable mechanical tapped density tester that p r o v i d e s a f i x e d d r o p o f 1 4 + / - 2 m m a t a n o m i n a l r a t e . The Carr index is frequently used in pharmaceutics as an indication of the flowability of a powder. A Carr index greater than 25 is considered to be an indication of poor flowability, and below 15, of good flowability. The Carr index is related to the Hausner ratio, another indication of flowability. Both the Hausner ratio and the Carr index are sometimes criticized, despite their relationships to flowability being established empirically, as not having a strong theoretical basis. Use of these measures persists, however, because the equipment required to perform the analysis is relatively cheap and the technique is easy to learn.

The disintegration test determines whether tablets or capsules disintegrate within a prescribed time when placed in a liquid medium under the prescribed experimental conditions. The disintegration of the drug active and the excipients is the major contributory factor in disintegration and dissolution. The more water-soluble the formulation, the quicker it disintegrates and releases the substance. In the case of substances which are poorly soluble in water, disintegration and release depend heavily on disintegrants and diluents.