Search

BR-102024027133-A2 - METHOD FOR PREPARING A DISPERSIBLE TABLET OF LISDEXAMPHETAMINE DIMESYLATE

BR102024027133A2BR 102024027133 A2BR102024027133 A2BR 102024027133A2BR-102024027133-A2

Abstract

This disclosure relates to a method for preparing a dispersible tablet of lisdexamfetamine dimesylate. The preparation method comprises: dry mixing lisdexamfetamine dimesylate, a diluent, a binder, and an antistatic agent to form a dry mix blend; intermediate granular mixing of a filler, a buffering agent, a disintegrating agent, and a sweetener to form an intermediate granular mix; adding and mixing the dry mix and the intermediate granular mix to form an intermediate drug mix; lubricating the intermediate drug mix with a lubricant to form compressible drug granules; and compressing the compressible drug granules to form a dispersible tablet of lisdexamfetamine dimesylate.

Inventors

  • MAHENDRA BALIRAM CHAUDHARI
  • OMPRAKASH DOULATRAM CHANDWANI
  • NITIN PANDHARINATH NEHETE
  • AMOL YUVRAJ CHAUDHARI
  • ANITA KUNAL SHAHANE

Assignees

  • ATHENA PHARMACEUTIQUES SAS

Dates

Publication Date
20260317
Application Date
20241223
Priority Date
20240903

Claims (10)

  1. 1. A method for preparing a dispersible tablet of lisdexamfetamine dimesylate, wherein the method is characterized in that it comprises: dry mixing lisdexamfetamine dimesylate, a diluent, a binder and an antistatic agent to form a dry mix blend; an intermediate granular blend of a filler, a buffering agent, a disintegrating agent and a sweetener to form an intermediate granular blend; adding and mixing the dry mix and the intermediate granular blend to form an intermediate drug blend; lubricating the intermediate drug blend with a lubricant to form compressible drug granules; and compressing the compressible drug granules to form a dispersible tablet of lisdexamfetamine dimesylate.
  2. 2. Method according to claim 1, characterized in that lisdexamfetamine dimesylate is present in an amount of about 8 to about 12 percent by weight.
  3. 3. Method according to claim 1, characterized in that, in the dry mixing step: the diluent is granular mannitol 200SD, and the diluent is present in an amount of about 18 to about 23 percent by weight; the binder is partially pregelatinized corn starch and the binder is present in an amount of about 10 to about 20 percent by weight; and the antistatic agent is anhydrous colloidal silica, and the antistatic agent is present in an amount of about 1 to about 2 percent by weight.
  4. 4. Method according to claim 1, characterized in that, in the intermediate granular mixing step: the filler is granular mannitol 200SD, and the filler is present in an amount of about 28 to about 34 percent by weight; the buffering agent is microcrystalline cellulose and the buffering agent is present in an amount of about 8 to about 12 percent by weight; the disintegrating agent is crospovidone, and the disintegrating agent is present in an amount of about 6 to about 10 percent by weight; and the sweetener is sucralose, and the sweetener is present in an amount of about 1 to about 4 percent by weight.
  5. 5. Method according to claim 1, characterized in that, in the lubrication step, the lubricant is magnesium stearate and the lubricant is present in an amount of about 1 to about 2 percent by weight.
  6. 6. Method according to claim 1, characterized in that the dosage amount of the lisdexamfetamine dimesylate dispersible tablet is 10 mg per tablet; 20 mg per tablet; 30 mg per tablet; 40 mg per tablet; 50 mg per tablet; 60 mg per tablet; and 70 mg per tablet.
  7. 7. Method according to claim 1, characterized in that the dissolution is not less than 75% in 15 minutes.
  8. 8. Method according to claim 1, characterized in that the friability is not more than 1.5%, the disintegration time is less than 3 minutes at 15°C to 25°C ± 2°C (without disc) and the hardness is from about 30 N to about 70 N.
  9. 9. Method according to claim 1, characterized in that the compression step employs the direct compression technique at a controlled moisture level of NMT 40% to reduce moisture exposure.
  10. 10. Method according to claim 1, wherein the method is characterized in that it further comprises packaging lisdexamfetamine dimesylate dispersible tablets in moisture-resistant removable ALU blister packaging; and/or moisture-resistant ALU-ALU blister packaging.

Description

FIELD OF PRESENT REVELATION [001] The present disclosure relates, in general, to a method of preparing a dispersible tablet. In particular, the present disclosure relates to a method of preparing a dispersible tablet of lisdexamfetamine dimesylate. BACKGROUND [002] Lisdexamfetamine dimesylate, the dimesylate salt of L-lysyl-d-amphetamine with molecular formula C17H33N3O7S2 is also known by the chemical name “(2S)-2,6-diamino-N-[(1S)-1-methyl-2-phenylethyl]-hexanamide, dimethanesulfonate”. The IUPAC name of lisdexamfetamine dimesylate is (2S)-2,6-diamino-N-[(2S)-1-phenylpropan-2-yl]hexanamide; methanesulfonic acid. [003] The chemical structure of lisdexamfetamine dimesylate is depicted in Formula I below: Lisdexamfetamine dimesylate is generally indicated for the treatment of moderate to severe Attention Deficit Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED) in adults. [004] Lisdexamfetamine dimesylate is a highly deliquescent material by nature, which when exposed to moisture by any means, absorbs the moisture and does not remain in solid form. [005] Lisdexamfetamine dimesylate is available on the market in capsule and chewable tablet form. A group of patients, such as geriatric patients, patients with mental retardation, uncooperative patients, patients with nausea, and patients with less than specific or personalized diets, etc., face difficulty swallowing lisdexamfetamine dimesylate in capsule or chewable tablet dosage forms. [006] During the last decade, there has been a need for a next generation of pharmaceutical products and drugs in multiple dosages that can be easily consumed, dissolve rapidly, and have the characteristics of dissolving, melting, or disintegrating in just a few seconds and providing the desired therapeutic result. The need also includes a suitable type of method for preparing the formulation that enhances the disintegration, dissolution, and free flowability of the components in the pharmaceutical form granule through physicochemical parameters adopted during the method. [007] Consequently, there is a need for a lisdexamfetamine dimesylate composition and dosage form that addresses the problem of lisdexamfetamine dimesylate deliquescence. Therefore, it is highly desirable to develop a rapidly disintegrating lisdexamfetamine dimesylate dosage form that allows for the rapid release of the drug from the granules and enables rapid absorption into the body after administration. Furthermore, it is desirable to develop a dispersible lisdexamfetamine dimesylate tablet that is stable, palatable, and disintegrates rapidly. Additionally, a method is needed where the processing time and production cost for preparing the lisdexamfetamine dimesylate composition are low. Furthermore, a process for a humidity-controlled manufacturing process is necessary to minimize the exposure of the deliquescent material to moisture during the production process. SUMMARY [008] To achieve the aforementioned and other objectives and needs, the present disclosure provides a method for the preparation of lisdexamfetamine dimesylate dispersible tablets and lisdexamfetamine dimesylate dispersible tablets prepared in this manner. The lisdexamfetamine dimesylate dispersible tablet developed by the inventor is a multi-dose quantity dispersible tablet that can be easily consumed, dissolves rapidly, and has the characteristics of dissolving, melting, or disintegrating in just a few seconds and providing the desired therapeutic result. The present disclosure provides a method for the preparation of a dispersible tablet that enhances the disintegration, dissolution, and free flowability of the granule components in the pharmaceutical form by its physicochemical parameters adopted during the method. [009] The present disclosure provides a synergistic combination of the API (active pharmaceutical ingredient) with excipients in a specific ratio to address the deliquescent nature of lisdexamfetamine dimesylate. The synergistic combination increases the disintegration time of the dispersible tablet. The present disclosure also confers improved palatability to the lisdexamfetamine dimesylate tablet formulation. The present disclosure provides a method of preparation with controlled humidity in which the tablet formulation is manufactured in a humidity-controlled environment to minimize the exposure of the deliquescent material to moisture during the production process. In particular, the manufacturing process employs direct compression techniques during the manufacturing process at controlled humidity levels of 40% NMT to reduce moisture exposure. [0010] The present disclosure provides a method for the preparation of lisdexamfetamine dimesylate composition for dispersible tablets that overcomes the disadvantages of solid compositions such as capsules and chewable tablets. The synergistic combination of the API with the excipients in a specific ratio is formulated to address the deliquescent nature of lisdexamfetam