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mixed amphetamine salts extended release (Adderall XR / Adderall, Microtrol / MAS XR)

✓ Approved

Shire · SLC18A2 · Small Molecule

What is mixed amphetamine salts extended release?

mixed amphetamine salts extended release is a small molecule developed by Shire. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesAdderall XR, Adderall, Microtrol, MAS XR
CompanyShire
Drug ClassSmall Molecule
Molecular TargetSLC18A2
RouteOral (PO)
StatusApproved

Mechanism of Action

Molecular Targets

mixed amphetamine salts extended release acts on 1 molecular target:

SLC18A2solute carrier family 18 member A2 (SVMT, VAT2)
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Therapeutic Indications

mixed amphetamine salts extended release is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Psychiatric disordersAttention deficit hyperactivity disorder✓ Approved

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Achieving an optimal balance between energy and stability remains a fundamental challenge in high-energy-density materials (HEDMs). Additionally, from a practical perspective, it is highly desirable to develop energetic materials via fewer and more efficient synthetic steps to facilitate broader applicability. In this context, the energetic salt formation strategy offers advantages over the corresponding neutral analogues by enabling comparable energetic properties through simpler synthetic routes. Herein, a dicationic precursor, 4-amino-3,5-bis(aminomethyl)-1,2,4-triazole (1), was synthesized in a single step from readily available starting materials. Subsequent reaction with energetic acids afforded a series of high-performing and physically stable energetic salts (3-7). These salts exhibit enhanced stability relative to analogous salts derived from previously reported 1,2,4-triazole-based cations. All compounds were thoroughly characterized by IR, NMR spectroscopy, and elemental analysis. Compounds 6 and 7 were confirmed through 15N NMR spectroscopy, while salts 5 and 6 were elucidated through single-crystal X-ray diffraction analysis. Additionally, Hirshfeld surface analysis and 2D fingerprint plots were employed to establish structure-property relationships.

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To fabricate and characterize extrudable polymeric matrices using a combination of ethyl cellulose (EC) and two different grades of hydroxypropyl cellulose (HPC) that can provide sustained drug release of the model drug salbutamol sulfate. Implementation of the Hot-Melt Extrusion (HME) technique in the fabrication of polymeric combinations that will provide ready-to-use matrices for sustained release dosage forms. Two formulation groups were developed; each with six formulations. The first group contained EC: HPC 370,000 ratios ranging from 55.52:13.8% to 6.9:62.46%, respectively. The second group contained EC: HPC 80,000 ranging from 59.4:10% to 9.4:60%, respectively. The release profiles were determined via in vitro studies to assess the ability of matrices to prolong salbutamol release. Solid-state characterization was also performed on the raw material and representative extrudates formulations using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) and polarized light microscopy (PLM). The first group formulations exhibited prolonged drug release profiles that accelerated progressively as the level of HPC 370,000 increased. In contrast, the second group formulations exhibited a noticeably faster release, demonstrating that HPC 80,000 can effectively accelerate drug release through enhanced matrix erosion and water penetration. DSC and XRPD revealed that the model drug remained in its stable crystalline state even after thermal processing via HME. PLM further confirmed drug crystallinity within the extrudates. EC-HPC matrices successfully demonstrated the feasibility of using HME to prepare sustained-release matrices for salbutamol sulfate with the ability to tune drug release by varying polymer grade and ratio.

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