Physical states of a pharmaceutical drug substance
Inventors
Audia, Vicki Haynes • Bristol, David William • Mitchener, JR., Joseph Pike • King, Clifford Riley
Assignees
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Publication Number
US-8039461-B1
Publication Date
2011-10-18
Expiration Date
Abstract
An amorphous form of imipramine pamoate, morphologically pure forms, and mixtures of amorphous and morphologically pure imipramine pamoate characterized by differential scanning calorimetry, fourier transform infrared, and powder x-ray diffraction, and pharmaceutical compositions formed therefrom.
Core Innovation
The document describes polymorphic and amorphous physical-state embodiments of imipramine pamoate, including amorphous imipramine pamoate and morphologically pure polymorphs identified as Forms I–VII, together with blends of amorphous material and one or more polymorphic forms. The polymorphic embodiments are defined and distinguished by solid-state characterization rather than by chemical identity.
Characterization is supported by DSC thermograms showing phase transition temperatures and heats of fusion, together with FTIR/IR absorbance spectra and PXRD diffraction patterns. The document also addresses PXRD diffraction analysis and includes identification of non-consequential sodium chloride peaks in the PXRD patterns.
The document further links the defined polymorphic and mixture embodiments to pharmaceutical compositions. The compositions are described as suitable for use in treating depression and neuropathic pain analgesic-like relief, and additionally include specified indications: fibromyalgia, childhood nocturnal enuresis, adult urinary incontinence, trichotillomania, post-traumatic stress disorder, and panic disorder.
Claims Coverage
The provided independent claims cover seven inventive features centered on imipramine pamoate polymorphs, blend preparation, and pharmaceutical compositions.
Polymorphic form defined by DSC phase transition and heat of fusion
A polymorphic form of imipramine pamoate having a differential scanning calorimetry (DSC) thermogram exhibiting a phase transition at about 140-170° C. and a heat of fusion of at least 15 Joules per gram.
Polymorphic form characterized by PXRD pattern of FIG. 23
A polymorphic form of imipramine pamoate characterized by a powder X-ray diffraction (PXRD) pattern as of FIG. 23.
Homogenous mixture preparation with analytical quality assessment
A process for preparing a mixture of polymorphic forms of imipramine pamoate comprising preparing selected forms, combining them in a pre-determined weight ratio, mixing to insure and assure homogenous intermixing, and assessing blend quality by DSC, infrared absorption (IR), PXRD, and chromatographic methodology.
Pharmaceutical composition comprising Form VII for specified therapeutic uses
A pharmaceutical composition comprising imipramine pamoate polymorphic forms wherein one form is imipramine pamoate Form VII suitable for use in treating depression, fibromyalgia, childhood nocturnal enuresis, adult urinary incontinence, trichotillomania, post-traumatic stress disorder, panic disorder, and to provide analgesic-like relief for neuropathic pain.
Pharmaceutical composition comprising at least one of Forms I–VII for specified therapeutic uses
A pharmaceutical composition comprising at least one material selected from imipramine pamoate Forms I–VII, adapted for use in treating depression, fibromyalgia, childhood nocturnal enuresis, adult urinary incontinence, trichotillomania, post-traumatic stress disorder, panic disorder, and to provide analgesic-like relief for neuropathic pain.
Pharmaceutical composition with specified amorphous-to-polymorph weight ranges
A pharmaceutical composition comprising 1 to 95 wt % amorphous imipramine pamoate and 5-99 wt % of at least one material selected from imipramine pamoate Form II, Form III, Form IV, Form VI, and Form VII.
Pharmaceutical composition selected by DSC phase transition and heat-of-fusion property sets
A pharmaceutical composition comprising at least one imipramine pamoate selected from specified phase transition ranges and associated heats of fusion.
Across the independent claims, the coverage centers on defining imipramine pamoate polymorphic forms by DSC thermogram phase transitions and heats of fusion, a specific polymorphic characterization by a PXRD pattern of FIG. 23, preparing homogenous polymorphic blends in pre-determined weight ratios with quality assessment by DSC, IR, PXRD, and chromatography, and using defined polymorphic forms or amorphous-containing blends in pharmaceutical compositions for specified therapeutic uses.
Stated Advantages
Suitable for use in treating depression, fibromyalgia, childhood nocturnal enuresis, adult urinary incontinence, trichotillomania, post-traumatic stress disorder, panic disorder.
Provides analgesic-like relief for neuropathic pain.
Documented Applications
Pharmaceutical use in treating depression.
Pharmaceutical use in treating fibromyalgia.
Pharmaceutical use in treating childhood nocturnal enuresis.
Pharmaceutical use in treating adult urinary incontinence.
Pharmaceutical use in treating trichotillomania.
Pharmaceutical use in treating post-traumatic stress disorder.
Pharmaceutical use in treating panic disorder.
Use to provide analgesic-like relief for neuropathic pain.
Preparation of a homogenous mixture of polymorphic forms of imipramine pamoate with assessed quality by DSC, IR, PXRD and/or chromatographic methodology.
Characterization of a polymorphic form using PXRD pattern as of FIG. 23 and, in refinement, using an IR absorbance spectrum as of FIG. 24.
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