Process

#The present invention relates to a novel process for the preparation of an oral delivery device for a pharmaceutically active agent. In particular, the invention relates to a process for the preparation of an oral delivery device comprising a core which contains the active agent, having a coating with one or more openings leading toward such a core.

#There is a requirement in the art to prepare oral delivery devices comprising a core which contains a pharmaceutically active agent, and having a coating with one or more openings leading to such a core. In particular, there is requirement to prepare such devices that can be used to deliver a drug substance, at a controlled rate of release, to an environment of use. Some of the devices utilised for this purpose are discussed in U.S. Pat. No. 5,004,614, which particularly relates to a controlled release device with an impermeable coating having an orifice for release of drug when the device has been orally administered and is immersed in an aqueous medium such as gastro-intestinal fluid. The impermeable coating of such a device may be applied to a tablet core according to standard pharmaceutical formulations (e.g. dip coating, compression coating etc.) and the orifice formed by removing sections of the formed coating by laser or mechanical drilling.

#It has now been found that one or more openings of various size and shape may be formed in an oral delivery device more rapidly and accurately than that provided by known drilling techniques. Thus, it is an object of this invention to provide an alternative process for the preparation of oral delivery devices having a coating with one or more openings leading to a tablet core. It is a particular object of this invention to provide an improved process for the manufacture of devices of the type disclosed in U.S. Pat. No. 5,004,614, the contents of which are incorporated herein by reference. It is also an object of the invention to provide novel constructions of devices of this general type. Other objects and advantages of the invention will become apparent from the following description.

#The invention will now be described by way of example only with reference to the accompanying drawings in which:

#FIG. 1 shows a suitable horn for making a device of this invention, in longitudinal and cross sections;

#FIG. 2 shows a fully coated core comprising a pharmaceutically active drug substance and excipients;

#Referring to FIG. 1, the horn 20 is made of titanium, and comprises a generally cylindrical shaped tubular part narrowing to a tip 21 at a distal end. The tip 21 is ring-shaped in cross section, corresponding in shape to the cross section of the member 20, and is profiled into a sharp edge 22 (machined as sharp as possible) having parallel, i.e., cylindrical, outer sides. Longitudinally along the center of the horn 20 is a bore 23, which may be connected to a vacuum line (not shown). Adjacent its open end 24, the bore tapers conically at a conical angle of ca. 7°, this profile being found suitable for effective cutting of the opening. Further downstream from the end 24, the internal bore widens internally, and from this wider part a side conduit 25 extends laterally. Around the tubular part, adjacent the side conduit 25, is a sleeve 26, with a bore closely conforming to the outer profile of the tubular part 20, and having a bore 27, which serves as a sleeve conduit, extending through its wall and leading to a vacuum connection 28. Between sleeve 26 and tubular part 20 are elastomeric ring washer seals 29 located respectively proximally and distally from side conduit 25 and from bore 27. At its proximal end 210, opposite the tip 21, the horn 20 is connected by a standard coupling 30 to a known ultrasonic generator 31 for applying ultrasonic energy to the horn 20. The ultrasonic generator utilized was a Rainbow Ducane DEC Press System.

#Referring to FIG. 2, a device is shown 10 overall comprising a compressed core 11 that is suitable for use in a controlled release formulation, and which consists of 10% of a pharmaceutically active ingredient, 40% hydroxypropylmethyl cellulose (HPMC), 29% lactose, 20% microcrystalline cellulose and 1% magnesium stearate. The core 11 is made by mixing together the listed ingredients and compressing using a conventional powder compression process. The core 11 is entirely surrounded by a coating 12 which is 10% (of total weight of core and coating) of ethylcellulose, applied using a typical tablet coating process. As coated, the tablet is of a bi-convex shape having upper and lower domed sides and a circular horizontal section cut perpendicular to the plane of the drawing. The device is approximately 10 mm diameter in its circular cross section and about 4 mm thick, and the coating layer is approximately 150 microns thick.

#In use the device 10 is securely supported, and the tip 21 of the horn is applied to the coating at a point 13 at the centre of one of the domed surfaces. Ultrasonic energy is then transmitted to the horn and then the tip 21 is pressed gently against the coating 12. The horn utilises a half wavelength resonance section at 18-55 KHz, preferably ca. 40 KHz, and is set to have an amplitude in the longitudinal direction of 60 microns peak to peak, maintained by the operating power of 50-100 W. Amplitude is measured as a percentage, a transducer in the system converting electrical energy to mechanical energy, to an output of 10 micron. The mechanical energy is then transferred to the booster of a particular ratio (e.g. 3:1) which increases the mechanical energy, this energy is finally transferred to the horn which again increases the mechanical energy. The amplitude is the percent of this mechanical energy and in the art is a common way of expressing the set up of the system. Such operating conditions are easily within the normal operating parameters of the system. set by the operating power of 50-100 W. Such operating conditions are easily within the normal operating parameters of the system.