Suppositories content uniformity

Suppositories Enemas Pessaries Vaginal solutions Biopharmaceutics Formulation Preparation Hard fat Content uniformity... 

In suspension suppositories, the active substance is processed as small particles that are prone to form agglomerates. The effective dispersion of the agglomerates (see Sect. 29.3) is a prerequisite for a sufficient content uniformity. Lactose may be used in pharmacy preparations to disperse the agglomerates and to maintain separation of the primary particles. This is most important with low dosed active substances, which do not easily lead to a good content uniformity. If 50 mg or less of active substance(s) is used per suppository, as a standard 100 mg lactose may be added to each suppository, as illustrated by chlorpromazine suppositories in Table 11.4. The added lactose should not be considered as a filler only as it is in tablets or capsules, but its main function in suppositories is the dispersing of the active substance. 

In the preparation of suspension suppositories it is important that the used particles of the active substance are small and remain small (don t reagglomerate). Small particles being essential for a correct content and a sufficient content uniformity of the suppositories, dispersion of the active substance in the suppository base will usually be preceded by or combined with particle size reduction, see Sects. 29.2 and 29.3). Large primary particles should be ground and agglomerates should be broken up. If an active substance is not available in the required particle size, the coarse powder must be ground in a rough stone or porcelain mortar. Active substances kept in stock in the required primary particle size... 

Only if the suppository crmtains 25 mg or more of an active substance, comprising 25 % or more, by mass, of the suppository, the mass variatimi test is applicable instead of the content uniformity test For instance, in suppositories weighing about 2.0 g, the active substance should be 500 mg or more for the mass variatiOTi test A determination of the content uniformity will be needed for most suppositories. 

To obtain a good uniformity of content is the greatest challenge in the preparation of suspension suppositories and can only be achieved by a proper design of the (batch) preparation instruction and properly following it. So the outcome of determination of content uniformity is very relevant for the monitoring of the preparation process. 

Settling during pouring Is of little importance for the average content, but of significant importance for the content uniformity of separate suppositories, see 11.5.5... 

A suppository molding apparatus should be subjected to initial and periodical qualification and the molding process to validation. The precise method to execute the PQ depends on the formulation and batch size. A worst case scenario should always be defined and test processes should be executed with a suitable formulation. The test product should be mainly examined on content uniformity, weight uniformity, and appearance. 

The uniformity of content of suppositories with morphine hydrochloride 20 mg in a fat base is considerably improved by triturating the morphine hydrochloride first with 100 mg of lactose or mannitol [28]. It is likely that the agglomerates of morphine hydrochloride are ground between the crystals of lactose or mannitol into smaller primary particles. 

Insufficient mixing will usually result in insufficient content uniformity, but with complex processes such as the preparation of suppositories, it may even result in a deviation in the average content, see Sect. 11.8.3. 

Suppositories content, mean weight, content uniformity, appearance, microbial purity. 

The requirements and assay of average content has been discussed in Sect. 32.4. When a medicine consists of single dosage units, the contents of those separate units (tablets, capsules, suppositories)have to meet content requirements. The separate assay values are used for estimation of the average content but also to estimate the variation between the units (uniformity of content). The separate mass values also have to meet requirements. The mass variation may give some indication of the content variation. 

For the diclofenac sodium suppositories 12.5 mg the specifications of the product are outlined, together with information about the sources of these specifications. For the specification on the content of active substance may be referred to national laws, for a specification on the uniformity of dosage units referral may be made of the European Pharmacopoeia, but for the appearance own specifications may be used, for example no holes or cracks . 

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