Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1998-03-13
2000-09-05
Wilson, James O.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 25, 514 48, 514 53, 514951, A61K 3170
Patent
active
061143138
DESCRIPTION:
BRIEF SUMMARY
The present invention provides a pharmaceutical composition suitable for freeze-drying and a process for the preparation of the composition.
BACKGROUND OF THE INVENTION
Freeze drying is a well known process used to prepare storage stable formulations of pharmaceutical compounds which otherwise suffer degradation when stored in the presence of water, for example, because of disproportionation and/or hydrolysis. A typical freeze drying cycle consists of four stages. Freezing the composition of the compound to be freeze dried, a primary drying cycle which comprises applying a vacuum and sufficient heat to sublimate the ice present in the composition, a second drying cycle which removes any residual water and then recovery of the freeze dried composition. It is an expensive process because it takes a long time and because a low temperature and a vacuum are required. A low temperature is required because the vacuum needs to be applied at a temperature below the eutectic temperature for mixtures of crystalline substances or below the glass transition or collapse temperature for amorphous mixtures. This is to ensure that the water present is vapourised without passing through the liquid state and so that the amorphous mixtures do not collapse. A collapsed amorphous mixture is effectively useless because it is very difficult to reconstitute and may be unstable.
To keep costs down it is preferable for the collapse or eutectic temperature not to be too low in order that the cooling cost is reduced. A higher collapse or eutectic temperature is also advantageous because the evaporation is hastened which reduces the length of time the vacuum is needed. Compositions suitable for freeze drying have been sought which produce a stable product and for which the collapse or eutectic temperature is not too low.
DESCRIPTION OF THE INVENTION
According to a first aspect of the invention there is provided a pharmaceutical composition comprising a nucleotide analogue, mannitol and a modifying additive which is sodium chloride or a polyol.
The invention further provides a pharmaceutical composition in freeze dried, spray dried or vacuum dried form and in reconstituted form.
According to the invention there is further provided a process for the preparation of a composition according to the invention which comprises mixing the ingredients of the composition, and either freezing them and drying the frozen mixture, or spraying them (for example into warm air).
The use of the combination of mannitol and the modifying additive in the compositions of the invention has unexpectedly been found to improve the compositions long term stability after freeze drying. Another advantage of using such a combination is that vial breakage or cracking during freeze-drying is prevented.
A nucleotide is a compound comprising a purine or pyrimidine base attached to a pentosugar wherein one or more of the hydroxy groups of the pentosugar are phosphorylated by a mono- or polyphosphate. A nucleotide analogue for use in the invention is in general a compound in which one or more of the three moieties of which a nucleotide is comprised is modified, for example, by attachment of one or more substituents and/or by replacement of one or more of the skeletal atoms.
The nucleotide used in the invention is preferably a nucleotide from WO 94/18216 , that is to say a compound of formula (I): ##STR1## wherein R.sup.1 and R.sup.2 independently represent hydrogen or halogen, R.sup.3 and R.sup.4 independently represent phenyl, or C.sub.1-6 -alkyl optionally substituted by one or more substituents selected from OR.sup.5, C.sub.1-6 -alkylthio, NR.sup.6 R.sup.7, phenyl, COOR.sup.8 and halogen, R.sup.5, R.sup.6, R.sup.7 and R.sup.8 independently represent hydrogen or C.sub.1-6 -alkyl, and X represents an acidic moiety, or a pharmaceutically acceptable salt thereof.
Compounds of formula (I) may exist in tautomeric, enantiomeric and diastereomeric forms, all of which are included within the scope of the definition.
Pharmaceutically acceptable salts of the compounds of for
Bland Chris
Steele Gerald
Astra Zeneca UK Limited
Wilson James O.
LandOfFree
Pharmaceutical compositions for freeze drying does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical compositions for freeze drying, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical compositions for freeze drying will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2212255