Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Patent
1997-01-07
1998-10-06
Phelan, D. Gabrielle
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
424489, A61F 1300
Patent
active
058173323
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/FI95/00358, field June 20, 1995.
FIELD OF INVENTION
This invention relates to transdermal drug delivery using polymeric devices. Specifically the invention relates to a transdermal system in which steady-state drug release can be modified over a wide range.
DESCRIPTION OF PRIOR ART
Transdermal delivery is a feasible alternative route of drug administration for many drugs. Typically the drug delivery devices are based on non-porous polymers that determine the rate of drug release. The systems can, for example, comprise a drug reservoir surrounded by a polymeric membrane or a polymer matrix in which a drug is dissolved or dispersed.
Typically drug release from a transdermal delivery system is controlled by the ability of the drug to partition with respect to the rate-limiting polymer and by its diffusivity in the polymer membrane or matrix. Partitioning with respect to the membrane can be modified by the partitioning coefficient of the drug between the reservoir and the rate-limiting membrane. Diffusivity in the membrane or matrix can be controlled by the chemical and physical structure of the membrane or matrix.
The conventional reservoir device technology has some drawbacks when the drug that is to be delivered transdermally is a weak base or a weak acid. Firstly, most weak acids and weak bases are more stable in the form of their crystalline salts. Due to their polarity salts can not partition into the release rate limiting nonporous polymers and thus they are not released from the device. Secondly, when free acids and bases are used in the delivery devices they partition during the storage in the release rate limiting polymers. This causes an unpredictable rise in drug concentration in the membranes and an initial high rate of drug release after application of the device. Clinically the initial release burst may be desirable or undesirable depending on the drug. The initial release burst shortens the time delay before steady drug levels are achieved in the body, but at the same time skin irritation by some drugs may be intensified.
An attempt to overcome the problems relating to the storage of drugs which are weak acids and weak bases is described in U.S. Pat. No. 4781924. This patent discloses a transdermal system where the therapeutic agent, which in the active form is either an acid or a base, during the storage of the preparation exists as a salt which is not able to migrate 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 powder form during storage. When the transdermal preparation is placed on the skin, moisture from the skin 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 system described above is an essential improvement with respect to the storage problems, but in many cases dissolution rate of the solid drug particles may become rate-limiting factor in drug release. Due to this drug release rate can not be controlled by the activating agent.
Steady-state release of weak bases/acids can be controlled by using appropriate pH-adjusting buffers. Release rate of drugs from transdermal systems can be controlled over a range of orders of magnitude by devices in which anhydrous drug salt and suitable pH-adjusting buffer mixture are dispersed or encapsulated in non-porous polymer (Sutinen et al., Int J Pharm 62: 113-118, 1990). Upon imbibition of water in the system anhydrous drug salt and buffers are dissolved. Partitioning of the drug into the polymer and its rate of release are determined by the degree of ionization of the dissolved drug, which in turn is controlled by pH. Only the unionized form of the drug partitions into the polymer. However, drug solubility may cause problems and limit the applicability of buffers to release control. Poor solubility and slow dissolution rate of
REFERENCES:
patent: 4749574 (1988-06-01), Ueda
patent: 4756710 (1988-07-01), Bondi et al.
patent: 5120546 (1992-06-01), Hansen et al.
patent: 5324718 (1994-06-01), Loftsson
patent: 5403840 (1995-04-01), Vikmon
patent: 5438067 (1995-08-01), Jalonen et al.
"Development of a Novel Transdermal System Design", Ebert C.D. et al., J. Controlled Release, vol. 6, 1987 Amsterdam, pp. 107-111, see p. 110, figures 7,9.
"Water-activated and pH-controlled release of weak bases from silicone reservoir devices", R. Sutinen et al., International Journal of Pharmaceutics, 62 (1990) 113-118.
Paronen Timo P.
Sutinen Marja R.
Urtti Arto O.
LandOfFree
Transdermal 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 Transdermal drug delivery system, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Transdermal drug delivery system will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-74637