Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1999-07-15
2004-01-27
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S435000, C424S439000, C424S450000, C424S484000, C426S534000
Reexamination Certificate
active
06682756
ABSTRACT:
The present invention relates to an individually dosed active substance-containing and, in particular, aromatic(s)-containing film-shaped administration form rapidly disintegrating upon contact with a liquid, wherein the aromatic is present distributed as an internal, liposoluble phase, in the form of liquid droplets, in an outer, solid, water-soluble phase.
Flat administration forms to be applied in the oral region and on mucous membranes of the mouth are known. U.S. Pat. No. 3,444,858 describes medicament strips based on a gelatin-like material. Also, pharmaceutical products in the form of a film have already been described in the early 70s, such as, for example, in the New England Journal of Medicine, 289, 533-535 (1973). DE 24 49 865 describes medicinal active substance carriers in the form of a film, containing different active substances and active substance concentrations.
U.S. Pat. No. 4,128,445 discloses technical solutions in loading of carrier material with active substances, and in this context goes into the subsequent addition of active substance preparations by applying them onto pre-fabricated film-shaped preparations. The document describes loading methods in dry and moist form aiming at achieving a uniform, subsequent distribution of active substance on a layer.
The Canadian patent application No. 492 040 describes a process for manufacture of film-shaped preparations employing active substance along with gelatin, agar, gluten, carboxy-vinyl polymer, polyhydric alcohol, vegetable mucilage, wax or water.
Also known are proposals for application of active substance-loaded films or foils outside the pharmaceutical field. Thus, in EP 0 219 762 a water-soluble film of starch, gelatin, glycerol or sorbite is disclosed, which is coated using the roll coating method. In this connection, it is stated that such dosage forms may also be produced employing ingredients of chemical reagents, aromatics and the like.
DE 36 30 603 provides for a flat dosage form, on a carrier material (release film), to be peelable in doses.
Drug-containing film-shaped systems and their advantages are further known from U.S. Pat. No. 5,047,244, these systems comprising a double-layer structure of a water-swellable layer and a nonwater-swellable barrier film. The use of polymers such as polyethylene glycol, the use of colloidal silicon dioxide, of bioadhesive (e.g. carboxy-functional) polymers, but also of polyvinyl alcohol, and of a number of other auxiliary substances is likewise known from the above document.
A preparation suitable for making film-shaped aromatics-containing preparations is described by EP 0 460 588. A composition comprising 20 to 60%-wt. of film-former, 2 to 40%-wt. of gel former, 0.1 to 35%-wt. of active substance or aromatic, and a maximum of 40%-wt. of an inert filling agent is regarded as affording particular advantages. As a gel former, polyvinyl alcohol is mentioned besides other ingredients. However, as it turns out, the gel-forming properties of polyvinyl alcohol are only partially compatible with the film formers mentioned in this document. A portion of 20%-wt., and more, of film former—mostly a sugar derivative, polyethylene glycol, etc.—lead to considerable loss of aroma occurring already in thin-layer drying, which is part of the production process.
Microcapsules are known application forms for protection of volatile or incompatible, finely dispersed products by providing an enclosure with a solid phase (e.g. Bauer/Frömmig, Pharmazeutische Technologie, Stuttgart 1986, 563-566). In the case of microencapsulated aromatics, individual drops of liquid are made processable, e.g. free-flowing, by enclosing. Such forms have already been proposed for application in the oral region, for example according to U.S. Pat. No. 5,286,496. These are, however, fine-grained intermediate products for the manufacture of final products having greater dimensions.
Aromatics-containing sheet-like administration forms for application in the oral region are also known from EP 0 452 446. However, this document does not describe any measures for preventing evaporation of aromatic substance during manufacture and/or storage.
In U.S. Pat. No. 4,946,684 the use of sugar alcohols for increasing moisture stability has been proposed for such forms appearing as flat, solid, open-pored foams, although not for film-shaped forms. However, according to applicant's findings, in the processing of aromatics, the use of high portions of such solubility-increasing additives results in a higher loss of aroma.
Thus, the known methods of producing and assembling film-shaped carriers comprising aromatic ingredient are afflicted with basic disadvantages:
On the one hand, their mechanical strength is dissatisfactory; in particular, the flexural strength and tear resistance of the films obtained is not sufficient for routine applications that are user-friendly.
When adjusted to be softer, the films show the phenomenon of “cold flow”, that is they tend to conglutinate with each other. This property is of disadvantage since the user can no longer apply or dose these objects individually. The main disadvantage, however, is to be seen in the fact that aromatics-containing films according to the prior art, by reason of their structure and the selected auxiliary substances, are subject to considerable loss of aroma occurring during manufacture and storage. This loss is a consequence of the overall quantitative loss of aromatics due to migration/diffusion through the base material and subsequent evaporation. At the same time, the quality of the impression of taste is changed, since readily volatile, quality-determining single components are those which are most readily lost.
Based on the above prior art, the present invention has the object of providing an individually dosed administration form of the kind indicated in the introductory generic part of claim
1
; which administration form exhibits improved mechanical properties and minimal loss of aroma during production and storage thereof, while avoiding the above-mentioned disadvantages and difficulties.
This object is solved according to the present invention in accordance with the features of claim
1
. The active substance-containing internal phase, containing the aromatic substance in the form of liquid droplets, is enclosed in an outer, solid but water-soluble phase containing, in accordance with the characterizing portion of claim
1
, portions of polyvinyl alcohol, of surfactants and of filling agents, with the constituent amount of the internal phase being between 0.1 and 30%-wt., relative to the outer phase. Using considerable portions of polyvinyl alcohol, the aromatic is embedded within the film, thereby forming a two-phase system.
The administration form according to the invention disintegrates in the mouth within, at most, 5 minutes, and in the process releases the aromatics contained therein, making them available, preferably, for providing assistance in cosmetic, pharmaceutical and food-technology applications. The products obtained according to the invention are surface-stable, flexible and break-resistant, as well as being largely tear-resistant. The adhesion-reducing rough surfaces exhibit only little static friction and practically no “cold flow”.
Regularly, the object of the invention is achieved when the outer phase substantially consists of polyvinyl alcohol, and the constituent amount of the aromatics-containing inner phase relative to the outer phase is between 0.1 and 30% (w/w), preferably between 1 and 5% (w/w), in each case relative to water-free portions. Below a portion of 0.1%-wt. the phases are soluble in each other, above 30%-wt. the outer phase becomes fatty and does no longer result in film-formation.
By adding up to 30% (w/w) of a surfactant to the outer phase, it is possible to improve the homogeneity of the distribution of droplets and of the size thereof, which may be between less than 1 &mgr;m and about 100 &mgr;m. Adding up to 40% (w/w) of a filler does not eliminate the advantages of the invention, but widens the scope of
Horstmann Michael
Laux Wolfgang
Hochberg D. Peter
LTS Lohmann Therapie-Systeme AG
Mellino Sean
Page Thurman K.
Pulliam Amy E.
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