Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Capsules
Reexamination Certificate
2000-09-27
2003-02-04
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Capsules
C424S400000, C424S443000, C424S451000, C424S456000, C424S489000, C424S490000, C424S502000
Reexamination Certificate
active
06514526
ABSTRACT:
The present invention relates to starch capsules. More precisely, the invention relates to coated starch capsules and the manufacture of such capsules.
In oral medical treatment, it is often justifiable to direct the release of a drug at the area of the intestines on a spot-specific basis. Many drugs do not tolerate well the acidic conditions of the stomach or they irritate the mucous membranes of the stomach (even to the effect of causing corrosion of a different degree in long-term use). The intention is to direct such drugs in a controlled way to the small intestine or the large intestine where they are absorbed and/or take effect locally in the most efficient way. Oral dosing of new drugs with peptide and protein structures is also used with the intention to release drugs on the spot-specific basis (pharmaceutical peptides are acid-labile and are not absorbed until the large intestine). It has been predicted that the use of pharmaceutical peptides and proteins will increase, which has aroused the interest of pharmaceutical industry, among others, in spot-specific pharmaceutical preparations.
Traditionally, spot-specific pharmaceutical preparations (so-called entero preparations) are prepared in multiple stages by a film coating technique in which solid nuclei containing drugs—granules, pellets or tablets—are enveloped in a pH-sensitive polymeric capsule. The manufacture involves some multivariable processes that are difficult to control. According to present knowledge, entero preparations should rather be formulated into multiple-unit preparations, for example, into film-coated granules or pellets which are encased in a capsule coat. The migration of the small entero granules and pellets in the alimentary tract, which are released from the multiple-unit preparations, is not dependent on the food consumed or on the speed of emptying the stomach.
The transfer of drugs in the intestines should be possible all the way to the large intestine and, on the other hand, it should be possible to store them at room temperature. Several drugs on the market are sensitive to fluctuations in ambient conditions during storage (for example, humidity, light, oxygen, and temperature). During storage, the drug may decompose chemically (chemical impurities), leading to impaired quality and efficacy of the phrmaceutical product. During storage, the physical and pharmaceutical properties of the drug formulation can also deteriorate. As regards solid drug formulations, for example, the package rarely gives sufficient protection to a labile drug and drug formulation, but other manufacturing methods should be used to guarantee the quality of the pharmaceutical preparation.
The purpose of the present invention is to provide a certain type of protective capsule which can be used to protect drugs against ambient impact so that the quality and the efficacy of the drugs will not change before they reach their destination. The purpose of the protective capsule is to protect the drugs against physical and chemical decomposition so that the drugs keep at room temperature for rather long periods of time. Another purpose of the protective capsule is to give protection against the acidity of the stomach and bile acids as well as other conditions in the intestines so that the quality and the efficacy of the drugs keep in the intestines as long as is appropriate from the viewpoint of the medicine's effect.
The present invention is based on the surprising observation that capsules can be formed from starch granules which give the drugs exactly the desired protection.
International patent publication WO 89/04842 describes the use of starch granules as a carrier for absorbed functional compositions. The starch granules are treated with alpha-amylase or glucoamylase. The publication suggests that starch granules be used as adjuvants for antiperspirants or as bulking agents for foods and drinks. It suggests that liquid substances be formulated, by using treated starch granules, into a powder, paste or cream formulation which is easier to pack or otherwise more practical. To strengthen the structure of hydrolyzed starch granules, the publication suggests treatment of the starch with cross-linking agents, such as sodium trimetaphosphate. If the substance to be absorbed into the starch granules has a lipid character, the starch matrix can, according to the publication, be treated with substances that render the pore surfaces more lipophilic. Such substances include, for example, synthetic polymers such as methylcellulose. The publication mentions that the substances to be absorbed can be, for example, salad oils, flavours, insect repellents, insecticides, herbicides, perfumes, moisturizers, soaps, waxes, body creams and lotions, vitamins and therapeutic drugs.
U.S. Pat. No. 5,670,490 describes porous aggregates formed of starch granules with the aid of binding agents, the empty space inside the aggregates being used to carry various functional substances. The substances are released from the aggregate under the influence of mechanical compression/decomposition, by disintegration of the binding agents or other substances, or by dissolution or diffusion from the porous surface. The diameter of the round aggregates was 15-150 &mgr;m. Typically, the binding agent was a polymer. The patent suggests the use of aggregates in formulating orally dosed pharmaceutical compounds, among others, so that the formulation protects the active ingredients against the acidic and decomposing conditions of the stomach and that the active ingredients would not be released until the small intestine. The aggregates were prepared by suspending the starch granules in a suitable solution containing binding agents and by spray drying the suspension. According to the publication, the aggregates could be coated with a polymer after putting the functional compounds inside the aggregates. The binding agents could be biodegradable polymers, such as polysaccharides (gums originating from algae or plants, pectins, agar-agar, alginate, gelatine, dextrin, starch derivatives) and cellulose-bearing substances, such as carboxy-methyl cellulose, hydroxy-methyl cellulose, hydroxy-propyl cellulose, etc., proteins, particularly those which are not inherently present in starch granules, as well as polyesters. The polymers could also be non-biodegradable, synthetic or semi-synthetic, such as polyvinyl alcohol poly-N-vinyl-2-pyrrolidone or polymers or copolymers of acrylic or methacrylic acid or their amide derivatives, such as polyacrylamide. The coating substances could be the same or different polymers than the binding agents. The functional substances that could be absorbed into the aggregates could be the same substances as listed in application WO 89/04842.
U.S. Pat. No. 4,551,177 describes a compressible starch that can be used as a binder for tablets. Cold-water-insoluble granular starch was treated with acid, alkali or alpha-amylase, whereby altered, weakened granules were obtained which, when compressed, showed a good binding capacity.
Patent publication EP 0 539 910 A1 describes the treatment of starch granules with an amylase. The intention was to modify the viscosity of the starch granules. The publication suggests that the amylase-treated starch granules be used in instant liquid food, for example, or as mixed with non-treated starch granules, whereby blends of starch granules having various viscosity values can be obtained. According to the publication, the amylase-treated starch granules adsorb hydrophobic substances such as aromatic compounds. The publication states that glucoamylase-treated starch granules are able to adsorb oils.
The publication of Milosevic et al., Journal of Controlled Release 38 (1996) 75-84, describes the use of amylose films to protect pharmaceutical preparations. According to the publication, insoluble polymers, such as ethyl cellulose, were used to control the swelling and decomposition of the amylose and, thus, the releasing speed of the drug in conditions that simulated the conditions of the alimentary tract. Accordi
Forssell Pirkko
Heinämäki Jyrki
Myllärinen Päivi
Palviainen Päivi
Poutanen Kaisa
Evans Charesse
Page Thurman K.
Valtion teknillinen tutkimuskeskus
LandOfFree
Coated starch capsules and a process for producing them does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Coated starch capsules and a process for producing them, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Coated starch capsules and a process for producing them will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3151760