Preparation containing 6,7-unsaturated-7-carbamoyl morphinan derivatives
Inventors
Mashimo, Akira • Ichio, Shunji • Tamura, Yoshinori • Noguchi, Kouichi
Assignees
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Publication Number
US-12350377-B2
Publication Date
2025-07-08
Expiration Date
Abstract
The solid preparation which improved the dissolution profile and the stability of the 6,7-unsaturation-7-carbamoyl morphinan derivative is provided. When 6,7-unsaturation-7-carbamoyl morphinan derivative, croscarmellose sodium and ferric oxide were contained, not titanium oxide in the solid preparations and the coating solid preparations, a dissolution rate after 15 minutes of the dissolution test is more than 85%, and stability, particularly, light stability can be improve.
Core Innovation
The invention relates to a coated solid preparation comprising a p-toluenesulfonic acid salt of a compound represented by formula (IA) as an active ingredient, with croscarmellose sodium and D-mannitol. The coated solid preparation comprises a core and a coating layer comprising hydroxypropylmethylcellulose, talc and ferric oxide.
The coated solid preparation is characterized by material exclusions. The coating layer does not substantially contain titanium oxide, and the core does not substantially contain ferric oxide.
The preparation is defined by dissolution performance measured using a dissolution test according to a paddle method of the Japanese Pharmacopeia in a test liquid having a pH of 6.8, with a dissolution rate after 15 minutes of more than 85% and a dissolution rate after 5 minutes of more than 60%. The document further supports light stability enhancement, including an increased light stability described through relative substances and light conditions.
Supporting disclosures describe the selection and placement of ferric oxide, including ferric oxide in a core and/or in a coating layer, and an emphasis that titanium oxide increases light-driven relative substances, while ferric oxide is used to reduce such increase and support discriminability.
Claims Coverage
The document provides one independent claim (clm-00001) defining a specific coated solid preparation with five inventive features, including ingredient selection, core/coating composition, exclusions regarding titanium oxide and ferric oxide placement, and defined dissolution performance in a Japanese Pharmacopeia paddle method at pH 6.8.
Coated solid preparation with formula (IA) p-toluenesulfonic acid salt
A coated solid preparation comprises a p-toluenesulfonic acid salt of a compound represented by formula (IA) as an active ingredient.
Core and coating layer composition with disintegrator and D-mannitol
The coated solid preparation comprises croscarmellose sodium and D-mannitol, and comprises a core and a coating layer comprising hydroxypropylmethylcellulose, talc and ferric oxide.
Substantially excluded titanium oxide in the coating layer
The coating layer does not substantially contain titanium oxide.
Substantially excluded ferric oxide in the core
The core does not substantially contain ferric oxide.
Paddle-method dissolution performance at pH 6.8
A dissolution rate after 15 minutes of a dissolution test according to a paddle method of the Japanese Pharmacopeia in a test liquid having a pH of 6.8 is more than 85% and a dissolution rate after 5 minutes of a dissolution test according to the paddle method in a test liquid having a pH of 6.8 is more than 60%.
Overall, the claim coverage focuses on a coated solid preparation using a specific formula (IA) p-toluenesulfonic acid salt, a defined core/coating structure with hydroxypropylmethylcellulose, talc and ferric oxide in the coating, disintegrator and D-mannitol inclusion, material exclusions for titanium oxide in the coating layer and ferric oxide in the core, and defined early dissolution rates in a Japanese Pharmacopeia paddle method at pH 6.8.
Stated Advantages
Improved early-stage dissolution as evidenced by dissolution rates after 5 minutes and after 15 minutes in a paddle method at pH 6.8.
Enhanced stability, especially light stability, supported by disclosures relating titanium oxide to increased light-driven relative substances and ferric oxide to reducing such increase.
Documented Applications
Coated solid pharmaceutical preparation with a core and coating layer for a p-toluenesulfonic acid salt of a compound represented by formula (IA), formulated to meet specified dissolution performance in a Japanese Pharmacopeia paddle dissolution test at pH 6.8.
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