Oral transmucosal drug delivery system
Inventors
Ahmed, Salah U. • Zu, Yanming • Neelam, Karunakar • MUNTAZIM, Saad • Chowdhury, Tahseen A. • TIAN, Shiying
Assignees
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Publication Number
US-10821118-B2
Publication Date
2020-11-03
Expiration Date
Abstract
This invention relates to dosage forms for the delivery of drugs across the oral mucosa having improved transmucosal permeability. More specifically, the invention relates to an oral transmucosal dosage form comprising a primary vehicle comprising a crystallization inhibition agent (CIA) system and a drug, and a secondary vehicle. It also relates to methods of designing and making this dosage form, methods of administering this dosage form and methods of packaging the dosage forms.
Core Innovation
The invention relates to an oral transmucosal dosage form comprising testosterone and a crystallization inhibition agent (CIA) system that includes a primary vehicle and a secondary vehicle. The CIA system reduces or controls drug crystallinity and prevents recrystallization.
The dosage form does not adhere to a specific location in the buccal area and erodes in about 10 minutes to about 60 minutes. This combination is stated to increase transmucosal permeability and enable rapid erosion and drug release without requiring disintegration.
The disclosure includes design and characterization concepts for selecting CIA ratios and predicting decrystallization outcomes, including a methodology based on DSC and XRPD and a mathematical model using heat of fusion (ΔHf) and decrystallization potential. The disclosure also provides examples and embodiments for hydrophilic, lipophilic, and amphiphilic CIAs together with secondary vehicle components and oral solid formats such as lozenge, troche, tablet, and lollipop.
Claims Coverage
The independent claims identified in the provided material are clm-00001, clm-00018, and clm-00021. Across these independent claims, the inventive concepts are centered on orally administering a compressed solid transmucosal dosage form containing testosterone and a specified crystallization inhibition agent (CIA) system with defined buccal non-adherence and erosion timing, and in clm-00018 and clm-00021 additional dosing constraints and plasma fluctuation reduction.
Testosterone deficiency treatment with hydrophilic, lipophilic, and amphiphilic CIA and non-adherent erosion
Orally administering a compressed solid transmucosal dosage form comprising testosterone and a crystallization inhibition agent (CIA) where the CIA comprises a hydrophilic CIA selected from specified polyethylene glycol (PEG) solids and related hydrophilic materials; a lipophilic CIA selected from oleic acid, hydrogenated vegetable oil, cocoa butter, carnauba wax, beeswax, or mixtures; and an amphiphilic CIA selected from polyethylene glycol glycerides, vitamin E-TPGS, mono-, di-, and tri-esters of sucrose with fatty acids, lecithin, or mixtures, or any combination of I-III, wherein oral availability of the testosterone is higher compared with oral availability of a dosage form comprising testosterone and no CIA, wherein the dosage form does not adhere to a specific location in the buccal area, and wherein the dosage form erodes in about 10 minutes to about 60 minutes.
Testosterone deficiency treatment with daily testosterone dose and specified CIA composition
Orally administering a compressed solid transmucosal dosage form comprising testosterone and a crystallization inhibition agent (CIA) at a dose of between about 0.5 mg and 20 mg testosterone per day, wherein the CIA comprises a hydrophilic CIA selected from specified PEG solids (PEG with molecular weight ≥2000 solid at room temperature) and related hydrophilic materials; a lipophilic CIA selected from oleic acid, hydrogenated vegetable oil, cocoa butter, carnauba wax, beeswax, or mixtures; and an amphiphilic CIA selected from polyethylene glycol glycerides, vitamin E-TPGS, mono-, di-, and tri-esters of sucrose with fatty acids, lecithin or mixtures, or any combination of I-III, wherein the dosage form does not adhere to a specific location in a buccal area and wherein the dosage form erodes in about 10 minutes to about 60 minutes.
Testosterone administration with 1 to 3 times per day for reduced plasma testosterone fluctuations using non-adherent CIA erosion dosage form
Orally administering a compressed solid transmucosal dosage form comprising testosterone and a crystallization inhibition agent (CIA) to a subject, wherein the oral transmucosal dosage form is administered 1 to 3 times per day and provides reduced fluctuations in plasma testosterone levels, wherein the dosage form does not adhere to a specific location in the buccal area of the subject, and wherein the CIA comprises a hydrophilic CIA selected from specified PEG solids (PEG with molecular weight ≥2000 solid at room temperature) and related hydrophilic materials; a lipophilic CIA selected from oleic acid, hydrogenated vegetable oil, cocoa butter, carnauba wax, beeswax, or mixtures; and an amphiphilic CIA selected from polyethylene glycol glycerides, vitamin E-TPGS, mono-, di-, and tri-esters of sucrose with fatty acids, lecithin or mixtures, or any combination of I-III, wherein the dosage form erodes in about 10 minutes to about 60 minutes.
Across clm-00001, clm-00018, and clm-00021, the independent claim coverage requires a compressed solid transmucosal dosage form with testosterone and a CIA system having specified hydrophilic, lipophilic, and/or amphiphilic CIA components, defined by non-adherence to a specific buccal location and erosion in about 10 to about 60 minutes. clm-00001 further requires higher oral availability versus a testosterone dosage form with no CIA, while clm-00018 and clm-00021 add daily dose or dosing frequency constraints and, for clm-00021, reduced plasma testosterone fluctuations.
Stated Advantages
Oral availability of testosterone is higher compared with oral availability of a dosage form comprising testosterone and no CIA.
Reduced fluctuations in plasma testosterone levels.
Documented Applications
Treating testosterone deficiency in a male subject in need thereof by oral administration of the compressed solid transmucosal dosage form.
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