THE PHARMACEUTICAL FORMULATIONS CONTAINING THE ANTIHYPERTENSIVE AND FORMULATION CONTAINING THE COMBINATION OF ANTIHYPERTENSIVE AND DIURETIC
Publication Date: 2008-Jan-17
The IP.com Prior Art Database
[1S-[1a,9a(R*)]]-9-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]octahydro-10-oxo-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid monohydrate is an oral antihypertensive (drug LC).
The drug is available in 0.5 mg, 1 mg, 2.5 mg and 5 mg immediate release film coated tablets.
As drug is sensitive to humidity several formulations were prepared (Examples in table 1).
Different technological procedures such as direct compression and dry or wet (i.e. water or organic solvent) granulation were used during formulation development.
Drug LC, lactose, hypromellose, maize starch, talc and sodium stearil fumarate were homogeneously mixed and compressed to cores. The obtained cores were coated with coating suspension prepared from hypromellose, talc, titanium dioxide, and purified water. Optionally iron oxide was added to coating suspension.
Drug LC, lactose, a part of hypromellose and a part of maize starch were homogeneously mixed and dry granulated. The remaining part of maize starch, the remain part of hypromellose, talc and sodium stearil fumarate were added to the previous granulate, mixed and compressed to cores. The obtained cores were coated with coating suspension prepared from hypromellose, talc, titanium dioxide, and purified water. Optionally iron oxide was added to the coating suspension.
The present drug LC can be also present in formulation with the combination with diuretic. For this reason additional formulations in form of film coated tablets were prepared. Beside the drug LC in those formulations also 6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulphonamide 1,1-dioxide (drug EH) as a diuretic was introduced (Table 2)
Drug LC, drug EH, lactose monohydrate, hypromellose and part of maize starch were mixed together and granulated with purified water to prepare the granulate (i.e. in examples A, C and H). The obtained granulate was dried until loss on drying less than 1.0% was achieved.
The dried granulate, maize starch, talc and sodium stearyl fumarate was compressed to a target core weight. Optionally drug EH, maize starch, talc, sodium stearyl fumarate can be added to dried granulate (i.e. examples B and G). The obtained cores were coated with coating suspension prepared from hypromellose, talc, titanium dioxide, iron oxide and purified water.
The primary packaging material for both types of formulations was blister packs consisting of cold formed OPA/Al/PVC film and heat sealing aluminium foil.
During the whole process controlled conditions with low humidity can be used.
Table 1: Compositions of formulation for Different Examples
Ingredient Examples - composition of film coated tablets (%)
0.5 mg 1.0 mg 2.5 mg 5 mg
A A1 B B1 C C1 D D1
Drug LC 0.38 0.38 0.76 0.76 1.26 1.26 2.52 2.52
Lactose Monohydrate 83.47 / 83.10 / 8...