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Synthesis and Regulation of Thyroid Hormones01:20

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Low blood levels of the thyroid hormones — triiodothyronine (T3) and thyroxine (T4) — signal the hypothalamus to release the thyrotropin-releasing hormone (TRH). TRH then reaches the pituitary gland and stimulates the release of thyroid-stimulating hormone(TSH) into the bloodstream.
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Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism01:21

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Polymorphism refers to the existence of a drug substance in multiple crystalline forms, known as polymorphs. Recently, this term has been expanded to include solvates (forms containing a solvent), amorphous forms (non-crystalline forms), and desolvated solvates (forms from which the solvent has been removed).
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The thyroid hormone (TH) plays a pivotal role in the intricate orchestration of physiological processes, exerting profound effects on development, metabolism, and homeostasis throughout different life stages.
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Changes in polymorphic forms can significantly influence the bioavailability of poorly soluble drugs. Although the FDA defines pharmaceutical equivalence based on having the same active ingredient, dosage form, and route of administration, it does not automatically disqualify products with different polymorphic forms. This means two products with different polymorphs can still be deemed pharmaceutically equivalent. However, polymorphic differences can affect properties like wettability,...
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Hormones can be classified into three main types based on their chemical structures: steroids, peptides, and amines. Their actions are mediated by the specific receptors they bind to on target cells.
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Structure Elucidation and Characterization of Different Thyroxine Polymorphs.

Santanu Mondal1, Govindasamy Mugesh2

  • 1Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore-560012 (India).

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|July 28, 2015
PubMed
Summary

Polymorphism in synthetic L-thyroxine (T4) affects its solubility and hormone activity. New polymorphs reveal conformational changes impacting halogen bonding and reactivity, crucial for thyroid hormone function.

Keywords:
halogen bondingiodinemetabolismpolymorphismthyroxine

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Area of Science:

  • Endocrinology and hormone regulation
  • Solid-state chemistry and materials science
  • Medicinal chemistry and drug design

Background:

  • Thyroid hormones, like L-thyroxine (T4), are essential regulators of numerous physiological processes.
  • Understanding the physical properties of synthetic T4 is critical for its pharmaceutical applications.
  • Polymorphism, the existence of different solid forms, can significantly alter drug solubility and bioavailability.

Purpose of the Study:

  • To report novel polymorphs of synthetic L-thyroxine (T4).
  • To investigate the impact of polymorphism on the solubility of T4.
  • To explore how conformational changes in T4 affect its chemical properties, such as halogen bonding and C-I bond reactivity.

Main Methods:

  • Synthesis and characterization of new L-thyroxine (T4) polymorphs.
  • Solubility studies of different T4 polymorphs.
  • Computational modeling and spectroscopic analysis to study conformational changes and their effect on chemical bonds.

Main Results:

  • Discovery and characterization of two new polymorphs of synthetic L-thyroxine (T4).
  • Demonstration that different polymorphs exhibit varying solubilities.
  • Identification of significant effects of conformational changes on halogen bond strength and C-I bond reactivity in T4.

Conclusions:

  • Polymorphism is a critical factor influencing the solubility of synthetic L-thyroxine.
  • Conformational variations in T4 significantly affect its chemical reactivity and potentially its biological activity.
  • These findings have implications for the formulation and therapeutic efficacy of thyroid hormone medications.