Hot-Melt Extrusion: Pharmaceutical Applications
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By clicking "I Agree", you confirm that you are above the age of 16, that you have read and understood the Privacy Policy and the Cookies Policy, and that you agree to the collection, use and processing of your Personal Information by Lonza in accordance with said policies. By Product Development Site. In these applications, the polymer is capable of kinetically stabilizing the API in the solid state and after exposure to a dissolving media. Similarly, crystalline solid dispersions can be prepared which exhibit improved wetting and dissolution characteristics.
Controlled release extrudates can be obtained by adding water insoluble our high molecular weight water soluble polymers into the processing mixture. Crystalline drug may be encapsulated with a polymer during processing. Similar approaches also can be used for the taste masking of drug substances. Jet milling is widely used in the pharmaceutical industry and remains the leading technology for particle size reduction and is most commonly used for having consistent and uniform particles during formulation.
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Spray congealing, also known as spray cooling, is a solvent free process that transforms a melt into well defined spherical particles. Spray drying has become one of the most successful particle engineering technologies for improving drug bioavalability through the amorphous solid dispersion platform. This is a proprietary Hovione technology for addressing complex particle reduction challenges. We offer a number of innovative particle engineering technologies, at all scales, to address recent challenges in drug delivery.
Hot Melt Extrusion
Would you like to take a few minutes to complete our short survey to let us know how we can improve your experience? The taste masking of bitter APIs is a major challenge especially for the development of orally disintegrating tablets ODT. More recently ibuprofen- and paracetamol-based taste masked formulations by HME have been reported [ 1 , 43 ]. In these studies, taste masking has been achieved through intermolecular forces e.
It was found that increasing IBU concentrations enhanced drug-polymer interactions as IBU has been found to present plasticising effects compared to traditional plasticizers. Later on the ground extruded materials were compressed in tablets and compared with commercially available Nurofen Meltlets Lemon ODTs and extruded tablets were found showing better taste masking efficiency as well as about 5-fold increased dissolution of poorly soluble IBU compared to that of Nurofen.
More recently Maniruzzaman et al. The taste evaluation of the developed formulations carried out by using an Astree e-tongue equipped with seven sensors and the generated data were analysed using multidimensional statistics. The data analysis showed significant suppression of the bitter taste for PMOL for both polymers. Actually in the forgoing study taste masking of bitter PMOL was strongly dependant on the nature of the polymeric carriers and the drug loading in the final formulation.
Additionally, in vitro taste analysis taste maps showed significant discrimination between placebo and extruded formulations Figure 5. The extrusion of solid lipids using twin-screw extruders was introduced for the preparation of immediate or sustained release taste-masked matrices [ 51 ]. Being divert from the polymeric extrusion the lipidic matrices offer several advantages over polymeric matrices during the extrusion process. In this study sodium benzoate was extruded with Precirol ATO5 glycerol distearate , hard fat, and stearic acid in order to mask the taste of API.
In this particular study the authors did not examine the masking efficiency of the manufactured lipid formulations which eventually made cold extrusion process questionable for the taste masking purposes. However, further evaluation of this process is a prerequisite until a considerable optimization is achieved for this method to be a viable taste masking approach.
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In these few studies, the effect of lipid composition and processing parameters such as the die diameter, the size of the extruded pellets, the screw speed, and the powder feeding rates on the obtained drug release patterns were thoroughly investigated. Very recently, Vaassena et al.
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The lipid-based formulations designed in this study was feasible for taste-masked granules or pellets containing poorly soluble drugs [ 52 ]. However, only a handful of researchers have reported the use of hot-melt extrusion for the manufacture of films. Films can be defined as thin sheets containing one or more polymers with or without a plasticiser and may be used as a drug delivery system device or directly applied to facilitate a therapeutic effect as in wound dressings.
Films are currently being produced mainly by solvent casting in which polymers and excipients such as plasticisers are dissolved in a suitable solvent until they form clear viscous solution gel. While film preparation using the solvent-casting approach allows film uniformity, clarity, flexibility, and adjustable thickness to accommodate drug loadings they are limited by decreased elongation or elasticity and increased film tensile strength when physical aging is applied [ 53 ].
Another limitation associated with solvent cast films is the use of organic solvents for water insoluble polymers. The hazardous nature of most organic solvents and the residual solvents after drying affect the selection of the appropriate solvent [ 54 — 57 ] as well as complicated processing conditions and disposal of the associated waste, all of which create significant environmental concerns.
As a result, alternative technologies are needed in the pharmaceutical industry to overcome some of the challenges described above. The two commonly used approaches include spray coating and hot-melt extrusion with the latter becoming increasingly popular due to the many advantages it provides. Firstly, no solvents are used and fewer processing steps are required. In fact one of the key advantages of HME is the fact that extrudates can be obtained in a single processing step making it very economical. As far as films are concerned, there is no requirement for compressing of the active ingredients together with the excipients.
The melting of the polymer into the molten state, coupled with the thorough initial mixing, allows a more uniform dispersion of fine particles. Further, molecular dispersion of the drug helps to improve its bioavailability [ 58 ]. Hot-melt extruded films are produced through a simple process involving blending of appropriate amounts of relevant polymer, drug, and plasticiser into a uniform powdered mixture prior to feeding through the hopper of the preheated extruder and transferred into the heated barrel by a rotating extruder screw.
Generally three main ingredients are required for successful formulation of hot-melt films, that is, film forming polymer, active ingredient, and plasticiser [ 59 ].
A Review of Hot-Melt Extrusion: Process Technology to Pharmaceutical Products
The latter is required to impart flexibility to the final film which ensures ease of handling and application to the site of action. Occasionally, other additives are added to affect other functionally important properties such as bioadhesive agent which ensures that the film adheres to the mucosal surface for a long enough time to allow drug absorption or action. Different polymers and drugs have been employed and reported in the literature for obtaining drug-loaded hot-melt extruded films for various indications and are summarised in Table 1. Repka and coworkers have conducted extensive research on the use of HME for the manufacture of mucoadhesive buccal films.
They successfully evaluated different matrix formers and additives for the processing of the blend prior to extrusion [ 60 — 63 ]. It has also been found that increasing the molecular weight of HPC decreased the release of drugs from hot-melt-extruded films which resulted in dissolution profiles exhibiting zero-order drug release.
According to the models applied in the research, the drug release was solely determined by erosion of the buccal film [ 65 — 67 ]. Development of films by HME may present future opportunities to develop gastroretentive films for prolonged drug delivery and multilayer films to modulate drug release for oral and transdermal applications.
The growing market in medical devices, including incorporating drugs into devices such as biodegradable stents and drug-loaded catheters, will undoubtedly require HME manufacturing processes.
These are required to be commercialised and perhaps may lead to new areas of collaboration across pharmaceutical, medical device, and biotechnology research. HME-related patents which have been issued for pharmaceutical systems have steadily increased since the early s. Despite this increased interest, only a handful of commercialized HME pharmaceutical products are currently marketed. Kaletra is mainly used for the treatment of human immunodeficiency virus HIV infections. The formulated, melt-extruded product was shown to have a significant enhancement in the bioavailability of active substances [ 70 ].
Furthermore, HME Kaletra tablets were shown to have significant advantages for patient compliance i. Additionally, Nurofen Meltlets lemon is available on the market as a fast dissolving tablet prepared by similar melting based technique [ 43 ].