1. Field of the Invention
The present invention concerns a special process for producing suppositories by compression, and the process of the invention is characterized by producing a suppository mixture granulate containing a considerably greater amount of active drug than ordinary suppositories as well as 20-50% by weight of a polyethylene glycol having an average molecular weight of at least 4000, and producing the suppositories in the same manner as tablets, i.e. by compression, instead of by moulding. The invention moreover concerns the suppositories obtained by the process which have a considerably higher percentual content of active drug than ordinary suppositories.
2. Description of the Prior Art
As will be known, suppositories are drugs intended for insertion into the rectum. They contain the active drug in a dosed amount and are produced by pressing, moulding or compression. They can also be produced in the form of capsules for controlled release of the active substance.
Ordinarily suppositories are produced by moulding, the produced mass being melted using the least possible amount of heat, and then the liquid mass is poured into moulds having the desired nominal capacity.
The suppositories produced by moulding are oblong and smooth, and they have a uniform appearance. Melting is intended to provide a uniform distribution of the drug in the basic mass, which, however, can be difficult to obtain because of sedimentation during hardening.
However, traditional moulding is a time-consuming and slow process which involves considerable costs. Moulded suppositories also have the drawback that too strong heating of certain suppository basic masses result in unstable modifications with a considerably reduced solidification point.
It is well-known to use polyethylene glycols having average molecular weights of 4000-6000 or above as the main component in the basic mass for suppositories produced by traditional melting and moulding. Thus, the DE Offenle-gungsschrift 2 248 777 describes melt-moulded indomethacin suppositories whose basic mass contains such polyethylene glycols.
It has previously been attempted to produce suppositories by compression or pressing, i.e. by traditional tabletting methods. However, these suppositories tend to form irregular rough surfaces, which makes them unpleasant to use for the patient. Moreover, in such a production method it has been found impossible to dose the drug in so high doses as is often desirable owing to the prescribed treatment.
Thus, the EP publication 111 137 describes suppositories containing the drug indomethacin in a base consisting of polyethylene glycol having an average molecular weight of up to 35,000. It is stated that the content of the active drug may be up to 50% by weight, but preferably the content is 2-40% by weight and in particular 2-26% by weight. All the examples in the publication concern rectal tablets having a content of indomethacin of 2.8-5.8% by weight and rectal capsules having a content of indomethacin of 5.25-10.5% by weight, i.e. rather low concentrations. Further, the suppositories thus known contain quite high amounts of polyethylene glycols, typically 1600-1730 mg per unit, which is a drawback, because it has been found that a content of polyethylene glycols in suppositories of 1-1.5 g per unit may cause bowel disorders.