Related Experiment Video
Updated: Mar 22, 2026
05:44
Formation of Dispersible Taohong Siwu Tablets
Published on: February 3, 2023
2.2K
Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation
V Vanhoorne1, B Bekaert1, E Peeters2
1Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
International Journal of Pharmaceutics
|April 21, 2016
Summary
Continuous twin screw granulation of delta-mannitol yields granules with superior tabletability due to a unique morphology. Process parameters influence the polymorphic transition and critical quality attributes, differing from less soluble excipients.
Area of Science:
- Pharmaceutical Technology
- Materials Science
- Chemical Engineering
Background:
- Mannitol is a preferred excipient for granulation due to its non-hygroscopicity and inertness.
- The delta-polymorph of mannitol undergoes a moisture-induced transformation to beta-mannitol, impacting morphology and tabletability.
- Continuous manufacturing processes offer advantages but require optimization for specific excipients.
Purpose of the Study:
- To investigate the influence of process parameters on critical quality attributes of granules and tablets during twin screw granulation of delta-mannitol.
- To understand the polymorphic transition of delta-mannitol to beta-mannitol under continuous granulation conditions.
- To compare the tabletability of granules produced from delta-mannitol versus beta-mannitol.
Main Methods:
- Full factorial experimental design applied to a ConsiGma™-25 continuous granulation line.
- Varied parameters included screw speed, granulation temperature, number of kneading elements, and liquid-to-solid ratio.
- Granules were dried, milled, and tableted; critical quality attributes and solid state were analyzed.
Main Results:
- The polymorphic transition from delta- to beta-mannitol occurred during twin screw granulation, influenced by L/S ratio, screw speed, and kneading elements.
- All granules exhibited a unique morphology associated with the polymorphic transition, leading to superior tabletability compared to beta-mannitol granules.
- Mannitol granulation followed a different mechanism than less soluble excipients due to its high solubility and dissolution rate.
Conclusions:
- Continuous twin screw granulation of delta-mannitol results in granules with enhanced plastic deformation and improved tabletability.
- Process parameter control is crucial for managing the polymorphic transition and achieving desired granule attributes.
- Mannitol's unique properties necessitate distinct granulation strategies compared to traditional excipients.
Related Concept Videos
01:21Factors Affecting Dissolution: Polymorphism, Amorphism and Pseudopolymorphism
826
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).
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
Some polymorphic crystals possess lower aqueous solubility than their amorphous counterparts, leading to incomplete absorption. For instance, the oral suspension of Chloramphenicol, which...
826
01:28Factors Influencing Drug Absorption: Pharmaceutical Parameters
740
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
740
01:18Formulation and Manufacturing Process: Physical Attributes of Generic Tablets and Capsules
400
Bioequivalence in generic drugs, such as tablets and capsules, refers to their pharmaceutical equivalence to the brand-name counterparts. However, for therapeutic equivalence, manufacturers must also consider physical attributes like size, shape, and weight (FDA Guidance for Industry, December 2003). Discrepancies in these aspects could impact patient compliance and cause medication errors. For instance, swallowing difficulties, often experienced with larger tablets or capsules, can lead to...
400
01:27Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
214
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,...
214
01:22Modified-Release Drug Delivery Systems: Rate-Programmed I
101
Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...
101
01:05Bioavailability Enhancement: Drug Stability Enhancement and GI Retention
305
Improving a drug's stability in the gastrointestinal (GI) tract is paramount for enhancing its bioavailability and therapeutic effectiveness. Various strategies are employed to protect the drug from the harsh gastric milieu and to ensure its release and absorption at the desired site within the GI tract.Polymer coatings are one such method used to shield drugs from the stomach's acidic environment. By preventing premature drug release, these coatings improve the bioavailability of unstable...
305