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Inhaled medications are crucial for managing chronic obstructive pulmonary disease (COPD) and asthma. They are essential for effective treatment and control, ensuring optimal respiratory health and well-being. Inhaled medication delivers drugs directly to the lungs, providing a rapid onset of action and reducing systemic side effects compared to oral or injectable medications. Three primary types of inhalation devices are used to administer these medications: nebulizers, metered-dose inhalers...
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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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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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Cholinergic antagonists—such as antimuscarinics—are available in oral, topical, ocular, parenteral, and inhalational formulations. Most antimuscarinics are oral formulations,  while scopolamine is available as a topical patch, and ipratropium and tiotropium are available as inhalation aerosols or powders. Atropine, tropicamide, and cyclopentolate are topically instilled in the eye. Most antimuscarinics are lipid-soluble and readily absorbed from the gastrointestinal tract and...
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Related Experiment Video

Updated: Oct 22, 2025

Author Spotlight: Developing a Disposable Dosator for Preclinical Testing of Dry Powder Inhalers in Small Animal Models
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Mannitol Polymorphs as Carrier in DPIs Formulations: Isolation Characterization and Performance.

Ayça Altay Benetti1,2, Annalisa Bianchera1, Francesca Buttini1

  • 1Department of Food and Drug Sciences, University of Parma, Parco Area delle Scienze, Building 8, 43124 Parma, Italy.

Pharmaceutics
|August 28, 2021
PubMed
Summary

Researchers explored D-mannitol polymorphs as dry powder inhaler carriers, finding specific crystal forms significantly impact drug aerosolization performance and are cytocompatible with lung cells.

Keywords:
DPI carrieraerosolizationbudesonidein vitro toxicityinhaler resistancemannitol polymorphssalbutamol sulphate

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Area of Science:

  • Pharmaceutical Sciences
  • Materials Science

Background:

  • Lactose is a common dry powder inhaler carrier, but limitations drive research into alternatives.
  • Carrier solid-state properties critically influence drug aerosolization in adhesive mixtures.

Purpose of the Study:

  • To crystallize kinetically stable D-mannitol polymorphs.
  • To evaluate the aerosolization performance of these polymorphs with model drugs (salbutamol sulphate and budesonide).
  • To assess the in vitro cytocompatibility of polymer-doped mannitol polymorphs with lung epithelial cells.

Main Methods:

  • Kinetically stable alpha and delta D-mannitol polymorphs were crystallized using polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP).
  • Aerosolization performance was tested using median and median/high resistance inhalers.
  • In vitro cytocompatibility assays were performed on lung epithelial cell lines.

Main Results:

  • The delta-mannitol form showed the poorest fine particle fraction for both hydrophilic and lipophilic drugs.
  • Alpha and beta-mannitol forms demonstrated comparable or superior aerosolization performance to lactose.
  • Recrystallized mannitol, PVA, and PVP exhibited good cytocompatibility with lung cell lines.

Conclusions:

  • Physicochemical properties of D-mannitol polymorphs can be leveraged to modulate carrier-drug interactions and optimize aerosolization.
  • Specific D-mannitol crystal forms offer promising alternatives to lactose for dry powder inhaler formulations.
  • Polymer-doped mannitol polymorphs are safe excipients for pulmonary drug delivery.