Process for preparing a lyophilised material

Abstract

A process for preparing a lyophilized material, providing a container having a penetrable envelope and containing the material in a carrier liquid, whereby the penetrable region is penetrated with a penetrator which provides a conduit through the envelope, and the carrier liquid id evaporated out of the container via the conduit, after which the penetrator is withdrawn. Apparatus suitable for performing the process is also disclosed.

1 . A process for preparing a lyophilised material comprising:
 providing a container bounded by an envelope having a penetrable region and containing a dispersion of the material in a carrier liquid,   penetrating the penetrable region with a penetrator such that the penetrator provides a conduit through the envelope to provide communication between the inside and outside of the container when the penetrator has penetrated the penetrable region,   evaporating the carrier liquid out of the container via the conduit, and   withdrawing the penetrator from the penetrable region.   
   
   
       2 . (canceled) 
   
   
       3 . The process according to  claim 1  wherein the container is a vial, having a mouth opening closed by an elastomeric closure, and the penetrable region comprises a region of this elastomeric closure. 
   
   
       4 . The process according to  claim 1  wherein evaporating the carrier liquid out of the container via the conduit is performed by
 maintaining the dispersion at a temperature such that the carrier liquid is frozen, and   applying reduced pressure so that the frozen liquid sublimates directly from the solid to the vapour state.   
   
   
       5 . The process according  claim 1  wherein the penetrable region comprises a previously-formed puncture hole in the penetrable region. 
   
   
       6 . An apparatus suitable for use in the process according to  claim 1  comprising:
 a penetrator capable of penetrating a penetrable region of a container bounded by an envelope having a penetrable region therein and containing a dispersion of the material in a carrier liquid such that the penetrator when penetrating the penetrable region provides a conduit through the envelope to provide communication between the inside and outside of the container when the penetrator has penetrated the penetrable region,   means to cause the penetrator to penetrate the penetrable region,   means to evaporate the carrier liquid out of the container via the conduit, and   means to withdraw the penetrator from the penetrable region.   
   
   
       7 . The apparatus according to  claim 6  wherein the penetrator comprises
 a generally tubular member having an end adapted to penetrate the penetrable region, and   one or more concavity in its outer surface   
     that provides a conduit between the penetrator and the adjacent surface of the penetrable region. 
   
   
       8 . The apparatus according to  claim 6  wherein the penetrator comprises a generally conical member with a opening adjacent its apex, an open base or an opening adjacent its base, and a conduit passing through the penetrator linking these two openings, such that its apex may penetrate the penetrable region and vapour of the carrier liquid may enter the apex, pass through the hollow interior of the conical member, and exit. 
   
   
       9 . The apparatus according to  claim 6  wherein the penetrator is mountable on a container so that the penetrator can be moved from a first position in which the penetrator is outside the container and does not penetrate the penetrable region, to a second position in which the penetrator penetrates the penetrable region. 
   
   
       10 . The apparatus according to  claim 9  wherein the penetrator is in combination with a guide, the combination comprising:
 a penetrator adapted to penetrate a penetrable region of the envelope of a container to thereby provide a conduit through the envelope to provide communication between the inside and outside of the container when the penetrator has penetrated the penetrable region, and   a guide which is mountable on a container to thereby support the penetrator   
     such that the penetrator can be moved from a first position in which the penetrator does not penetrate the penetrable region to a second position in which the penetrator penetrates the penetrable region, and optionally back toward a first position in which the penetrator does not penetrate the penetrable region. 
   
   
       11 . The apparatus according to  claim 10  wherein the penetrator comprises a generally conical member, and the guide comprises a generally cylindrical sleeve or part sleeve within which the penetrator is movable, and which may be mounted on a vial. 
   
   
       12 . The apparatus according to  claim 10  wherein the penetrator and the guide are made integrally of plastics material and are made initially linked by one or more thin frangible integral link with the penetrator in the first position, so that so that as the penetrator is moved from the first position toward the second position severance of the link occurs. 
   
   
       13 . The apparatus according to  claim 6  further comprising a lower shelf having an upwardly facing surface suitable for locating plural containers thereon, and a vertically adjacent upper shelf having a downward facing surface which comprises plural penetrators, the upper and lower shelves being moved relatively toward each other, so that the penetrators thereof are thereby moved reciprocally from a first position in which the penetrator does not penetrate the penetrable region, to a second position in which the penetrator penetrates the penetrable region, and optionally back towards a first position in which the penetrator does not at least partly penetrate the penetrable region. 
   
   
       14 . The apparatus according to  claim 13  wherein each penetrator comprises a generally conical member with its apex pointing downwardly from a lower surface of the upper shelf toward the lower shelf. 
   
   
       15 . The process according to  claim 1  performed in the following order:
 introducing the dispersion of the material in a carrier liquid into the container,   penetrating the penetrable region with the penetrator,   reducing the temperature of the liquid in the container until it is frozen,   evaporating the frozen liquid to thereby lyophilise the content,   allowing the temperature of the container to rise toward ambient temperature,   returning the pressure toward atmospheric, and   withdrawing the penetrator.   
   
   
       16 . The process according to  claim 15  wherein the container is a vial with an elastomeric closure, the penetrable region comprises a puncture hole in an elastomer vial closure, and wherein the process further of comprises sealing the residual puncture hole. 
   
   
       17 . An apparatus suitable for use in a process according to  claim 1  comprising:
 a penetrator adapted to penetrate the penetrable region of the envelope of the container to thereby provide a conduit through the envelope to provide communication between the inside and outside of the container when the penetrator has penetrated the penetrable region, and   a guide which is mountable on the container to thereby support the penetrator so that the penetrator can be moved from a first position in which the penetrator does not penetrate the penetrable region to a second position in which the penetrator penetrates the penetrable region, and optionally back toward a first position in which the penetrator does not penetrate the penetrable region.   
   
   
       18 . The apparatus according to  claim 17  characterised in that wherein the penetrator comprises
 a generally tubular member having an end adapted to penetrate the penetrable region, and   one or more concavity in its outer surface that provides a conduit between the penetrator and the adjacent surface of the penetrable region.   
   
   
       19 . The apparatus according to  claim 17  wherein the penetrator comprises a generally conical member with an opening adjacent its apex, an open base or an opening adjacent its base, and a conduit passing through the penetrator, such that its apex may penetrate the penetrable region and vapour of the carrier liquid may enter the apex, pass through the hollow interior of the conical member, and exit. 
   
   
       20 . The apparatus according to  claim 17  wherein the penetrator comprises a generally conical member, and the guide comprises a generally cylindrical sleeve or part sleeve within which the penetrator is movable, and which may be mounted on a vial having an elastomeric closure. 
   
   
       21 . The apparatus according to  claim 17  wherein the penetrator and the guide are made integrally of plastics material and are made initially linked by one or more thin frangible integral link with the penetrator in the first position, so that as the penetrator is moved from the first position toward the second position severance of the links occurs. 
   
   
       22 . An apparatus suitable for use in a process according to  claim 1  wherein the penetrator is itself mountable on the container in a position in which the penetrator is penetrating the penetrable region of the container. 
   
   
       23 . The apparatus according to  claim 22  wherein the penetrator comprises a generally conical member, and which is mountable on the container by means of a snap fit engagement. 
   
   
       24 . The apparatus according to  claim 22  wherein the penetrator comprises a conical member at least partly surrounded by a skirt extending in the cone base-apex direction, the skirt having snap-fit engagement means adjacent the rim furthest from the cone base.