Oral dosage forms are known which provide a zero order or first order release in which the drug is released at a substantially steady rate of release per unit of time. These dosage forms are satisfactory for the administration of pharmaceutical dosage forms of many drugs. However, there are instances where maintaining a constant blood level of a drug is not desirable. In such cases (e.g., optimization of chemotherapy, reducing nocturnal or early morning systems of chronic diseases such as ischemic heart disease, asthma, arthritis, avoiding developing a tolerance to nitrates, antibiotics and steroidal contraceptives, or where absorption windows exist), a ‘time-controlled’ pulsatile drug delivery system may be more advantageous. There are also instances in which a ‘position-controlled’ drug delivery system (e.g. treatment of colon disease or use of colon as an absorption site for peptide and protein based products) may prove to be more efficacious.
A pulsatile delivery system is capable of providing one or more immediate release pulses at predetermined time points after a controlled lag time or at specific sites. However, there are only a few such orally applicable pulsatile release systems due to the potential limitation of the size or materials used for dosage forms. Ishino et al. disclose a dry-coated tablet form in Chemical Pharm. Bull. Vol. 40 (11), p3036–3041 (1992). U.S. Pat. No. 4,851,229 issued Jul. 25, 1989 to P. R. Magruder et al., U.S. Pat. No. 5,011,692 issued Apr. 30, 1991 to K. Fujioka et al., U.S. Pat. No. 5,017,381 issued May 21, 1991 to Maruyama and R. Cortese, U.S. Pat. No. 5,229,135 issued Jul. 20, 1993 to F. Philippon et al., and U.S. Pat. No. 5,840,329 issued Nov. 24, 1998 to J. P.-F. Bai disclose preparation of pulsatile release systems. Some other devices are disclosed in U.S. Pat. Nos. 4,871,549 issued Oct. 3, 1989 to Y. Ueda et al., U.S. Pat. No. 5,260,068 and U.S. Pat. No. 5,260,069 both issued Nov. 9, 1993 to C. M. Chen and U.S. Pat. No. 5,508,040 issued Apr. 16, 1996 to C. M. Chen. U.S. Pat. No. 5,229,135 issued Jul. 20, 1993 and U.S. Pat. No. 5,567,441 issued Oct. 22, 1996 both to C. M. Chen disclose a pulsatile release system consisting of pellets coated with delayed release or water insoluble polymeric membranes incorporating hydrophobic water insoluble agents or enteric polymers to alter membrane permeability. U.S. Pat. No. 5,837,284 issued Nov. 17, 1998 to A. M. Mehta et al. discloses a dosage form which provides an immediate release dose of methylphenidate upon oral administration, followed by one or more additional doses spread over several hours. Thus there is a need for a pulsatile drug delivery system which is intended to provide for the simultaneous delivery of a single or a combination of drug substances as well as time-controlled series of pulses for efficacious treatment of diseases with maximum patient compliance and minimum side effects. Provision of a single targeted pulse several hours after oral administration, with or without an immediate release pulse upon oral administration, is a desired manifestation of the timed pulsatile release drug delivery systems of the present invention.
USPTO Backgrounds
USPTO Backgrounds