Wafer formulation

• US 8,623,401 B2
• Filed: 03/27/2008
• Issued: 01/07/2014
• Est. Priority Date: 03/27/2008
• Status: Active Grant

• Current Assignee: CTT Pharma Inc.
• Original Assignee: Fenwafe Inc.
• Inventors: Modi, Pankaj
• Primary Examiner(s): GULLEDGE, BRIAN M
• Application Number:
  US12/078,092
• Publication Number:
  US 20090246257A1
• Time in Patent Office: 2,112 Days
• Field of Search: 424/434, 424/435, 424/441, 424/443, 424/484, 514/777, 514/782, 264/160, 264/489
• US Class Current: 424/441
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

An orally administrable wafer is provided comprising at least one physiologically acceptable film forming agent. The wafer is formed by mixing the film-forming agent with an aqueous solution to form a gel and exposing the gel to a plurality of heating and cooling cycles. The wafer is rapidly dissolving and suitable for administration of pharmaceutical agents.

Claims

1. An orally administrable wafer comprising at least about 30 to about 80 wt % pullulan, PEG in an amount of less than about 5 wt % and a pharmaceutical agent selected from the group consisting of morphine, heroin, hydromorphone, metophon, oxymorphone, levorphanol, codeine, hydrocodone, oxycodone, nalorphine, naloxone, naltrexone and fentanyl, wherein the wafer is prepared by dissolving the film forming agent in an aqueous solution to form a gel that is treated with a plurality of heating and cooling cycles for a total time period of no more than about 3 minutes and the wafer exhibits a dissolution rate of at least about 2 milligrams/sec in an aqueous environment and a T_max of no more than about 10 minutes.

2. The wafer as defined in claim 1, additionally comprising one or more film forming agents selected from the group consisting of hydroxypropylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, carboxymethyl cellulose, polyvinyl alcohol, sodium alginate, glycolide, polylactide, polyacrylic acid, methylmethacrylate copolymer, carboxyvinyl polymer, amylose, high amylose starch, hydroxypropylated high amylose starch, dextrin, pectin, chitin, chitosan, levan, elsinan and mixtures thereof.

3. The wafer as defined in claim 2, comprising the film forming agents polyvinyl alcohol and carrageenan.

4. The wafer as defined in claim 1, additionally comprising one or more compounds selected from the group consisting of:

a plasticizing agent, a flavoring agent, a sulfur precipitating agent, a saliva stimulating agent, a cooling agent, a surfactant, a stabilizing agent, an emulsifying agent, a thickening agent, a binding agents, a coloring agent, a sweetener, and a fragrance.

5. The wafer as defined in claim 1, that exhibits a T_max of the agent on administration of the wafer to a patient of less than about 7 minutes.

13. A method of administering a pharmaceutical agent to a mammal comprising the step of orally administering to the mammal a wafer as defined in claim 1.

6. A method of preparing an orally administrable wafer comprising at least about 30 to about 80 wt % pullulan, PEG in an amount of less than about 5 wt % and a pharmaceutical agent selected from the group consisting of morphine, heroin, hydromorphone, metophon, oxymorphone, levorphanol, codeine, hydrocodone, xycodone, nalorphine, naloxone, naltrexone and fentanyl, wherein the wafer exhibits a dissolution rate of at least about 2 milligrams/sec in an aqueous environment and a T_max of no more than about 10 minutes, the method comprising the steps of:

1) mixing the pullulan and PEG with an aqueous solution to form a gel, and mixing the pharmaceutical agent with the gel; and

2) exposing the gel to a plurality of cycles, each cycle comprising heating and cooling, to transform the gel into a wafer, wherein the total time period of the cycles is no more than about 3 minutes.

7. A method as defined in claim 6, wherein each cycle comprises a period of heating up to a temperature within the range of 60-90°

C.

8. A method as defined in claim 6, wherein each cycle comprises a period of heating and a period of cooling, and each of said periods lasts about 5-15 s.

9. A method as defined in claim 6, comprising at least 3 cycles of heating and cooling.

10. A method as defined in claim 9, wherein the total time of the cycles is between about 1 and 2 minutes.

11. A method as defined in claim 6, wherein a measured amount of pharmaceutical agent is added to the gel to yield a wafer with a defined quantity of pharmaceutical agent therein.

12. A method as defined in claim 6, wherein the heating is achieved by exposure to microwaves.