Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Tablets – lozenges – or pills
Patent
1994-05-05
1996-05-21
Phelan, D. Gabrielle
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Tablets, lozenges, or pills
424469, 424481, 424485, 424489, 424490, 424496, A61K 922
Patent
active
055187374
DESCRIPTION:
BRIEF SUMMARY
FIELD
This application is a 371 of PCT/FI92/00274 filed Oct. 15, 1992.
This invention is related to peroral drug delivery of weak electrolytes. Specifically the invention describes a pharmaceutical product with a plurality of ingredients in which drug release can be modified over a wide range independently of the surrounding pH, osmotic pressure, and ionic strength.
BACKGROUND
Most drugs that are in clinical use are either weak bases, weak acids or their salts. Due to their pH-dependent solubility and dissociation, weak bases and weak acids have pH-dependent rates of drug dissolution. Substantial dissolution rate variations may become a problem in peroral drug delivery, if the compound has poor solubility in its un-ionized state and much higher solubility in its ionized state. pH varies considerably in the different parts of the gastrointestinal tract (between 2 and 7) and, thus, dissolution rate may also change during the transit of the dosage form in the gastrointestinal tract.
The pH may also vary in the stomach of an individual at different times relative to feeding. Also, the transit of the dosage form in the gastrointestinal tract has considerable interindividual and intraindividual variation. For the reasons mentioned above weak electrolytes may show dissolution rate controlled variations in their rates of absorption and consequently in their therapeutic activity.
Attempts to overcome the problem of pH-dependent variations in drug delivery include the development of osmotic pumps and buffered tablets (DE 2414868 and Theeuwes F., J. Pharm. Sci. 64: 1987, 1975). The osmotic devices are based on the osmotic influx of water from the surroundings into the device with high inner osmoticity. Water influx pushes drug solution from the dosage form through an orifice. Drug release from the osmotic devices is constant for a considerable period and it is not dependent on the surrounding pH. A disadvantage of these devices is that they are fairly complicated to manufacture and only drugs with high water-solubility can be used. In addition osmotic pumps have been known to adhere to the walls of the gastrointestinal tract causing severe local irritation.
In buffered tablets (DE 2414868) the drug crystals and solid-state buffer are mixed together so that during dissolution the microenvironmental pH in a tablet can be adjusted to be more favourable from the standpoint of drug dissolution. In these dosage forms drug release is controlled by microenvironmental pH. When the degree of drug ionization (and solubility) is increased with the buffer its dissolution rate is increased (DE 2414868). However, it should be remembered that the microenvironmental pH on the surface of drug crystal is in direct contact with bulk pH and bulk buffers. Consequently, it is affected by the surrounding bulk pH.
An attempt to overcome the problems relating to the storage in transdermal drug preparation of drugs which are weak acids or weak bases is described in U.S. Pat. No. 4,781,924. This patent discloses a transdermal system where the therapeutic agent, which in its active form is either an acid or a base, during the storage of the preparation exists in an inactive form, preferably a salt not being able to migrate out from the reservoir containing said therapeutical agent. The transdermal preparation further contains an activating agent, an acid or a base, which exists in an anhydrous form during storage. When the transdermal preparation is placed upon the skin, moisture from the human body diffuses into the system and converts the activating agent to the corresponding acid or base solution which further converts the salt form of the therapeutic agent to the corresponding free acid or free base.
The U.S. Patent cited above presents only the initial activation of the drug release. No ways to control the rate of drug release from the system have been demonstrated. Neither is there any suggestion that any similar phenomenon could or would work in oral preparations.
The present invention provides a controlled release device for peroral
REFERENCES:
patent: 4656027 (1987-04-01), Sjoqvist
patent: 4756710 (1988-07-01), Bondi
patent: 4781924 (1988-11-01), Lee et al.
patent: 4795644 (1989-01-01), Zentner
patent: 4968505 (1990-11-01), Okada et al.
Hawley's Condensed Chemical Dictionary, 12 ed, Richard J. Lewis, Sr, 1993, p. 455.
"Elementary Osmotic Pump", Felix Theeuwes, Journal of Pharmaceutical Sciences, vol. 64, No. 12, Dec. 1975, pp. 1987-1991.
Paronen Timo P.
Sutinen Marja R.
Urtti Arto O.
Orion-yhtyma Oy
Phelan D. Gabrielle
LandOfFree
Peroral drug delivery system does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Peroral drug delivery system, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Peroral drug delivery system will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2036082