Hot melt extrusion

Hot melt extrusion

1. HOT MELT EXTRUSION AN EMERGING DRUG DELIVERY TECHNOLOGY Monika Vasant Pawar M.Pharm - I Guided By : Dr . S.S.Mahajan 1

2. HOT MELT EXTRUSION Hot melt extrusion is a process of converting raw material into a product of uniform shape and density by forcing it through a die under controlled condition. 2

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4. MATERIAL USED IN HME API Polymers Additives Relevant characteristics of API Solubility Melting temperature Physical state Lipophilicity Thermal stability 4

5. Polymers : Selection by : Thermoplastic behaviour Suitable glass transition temperature (typically between 50-180°c) High thermal stability No toxicity Eg : Polyethylene glycol, Eudragit , Vinyl pyrollidone Additives : Physical state Plasticizing effect Lubricant effect Compatibility with API and polymer. 5

6. PLASTICIZER To improve processing condition,physical and mechanical properties of final product. To facilitate the extrusion and increase flexibility. Plasticizer reduces the Tg of the polymer Processing temperature and increase the stability. Shear forces Eg :Diethyl phthalate,PEG 400,Glycerol,Methyl paraben,Triacetin . 6

7. HOT MELT EXTRUSION Hot-melt extrusion (HME) is used for blending, melting, extrusion and shaping in a single step process. Extruders provide extensive mixing and agitation that causes de-aggregation of the suspended particles in the molten polymer resulting in a uniform dispersion. 7

8. PROCESS In hot-melt extrusion, a blend of polymer and excipients in powder form is transferred by a rotating screw through the heated barrel in the extruder. The molten mass is continuously pumped through the die at the end of the extruder and rapidly solidifying when exiting the machine. The screw itself is divided into three parts; feeding, melting and metering. In the feeding section, the material is transported from the hopper into the barrel. In the melting zone the polymer softens and melts, moving by circulation in a helical path. 8

9. In the metering zone, the pulsating flow is reduced to ensure a uniform delivery rate through the die cavity which is attached at the end of the barrel. 9

10. Extruder There are two types of extruders : single-screw and twin-screw extruders. Twin-screw extruders use two side-by-side screws either co-rotating or counter-rotating . There are several advantages of twin-screw extruders over single-screw extruders such as easier material feeding and dispersion capacities, less tendency to over-heat and shorter transit times . 10

11. Monitoring parameters 11

12. Characterization of extrudates Differential Scanning Calorimetry (DSC)- Differential scanning calorimetry (DSC) has been widely used to study the thermal properties of materials used in hot melt extrusion. DSC can be used for the quantitative detection of transitions (melting point, glass transition) in which energy is required or liberated (i.e. endothermic and exothermic phase transformations). The lack of a melting transition in the DSC scan of the hot-melt extrudate indicates that the drug is present in an amorphous rather than crystalline form. 12

13. Thermo Gravimetric Analysis (TGA) TGA is a measure of thermally induced weight loss of a material as a function of applied temperature. TGA is limited to studies involving either a weight gain or loss, and is commonly used to study desolvation and decomposition. TGA can be used as a screening tool for the thermal stability of materials used in hot-melt extrusion. 13

14. X-Ray Diffraction (XRD) XRD is also used to characterize the crystalline properties of hot-melt extruded dosage forms. XRD is commonly used to determine the solid state of the drug in an HME formulation immediately after processing and during storage, and to assess the impact on dissolution and bioavailabiliy . Microscopy : SEM is used to identify the microscopic structure of a dosage form and allow characterization of difference of crystal growth in the bulk and at the surface of a dosage form. Drug recrystallization was lower in extrudates containing polycarbophil & PVP compared to formulation without additives. 14

15. Infrared Spectroscopy (IR) IR can be used to detect changes in bonding between functional groups due to structural changes or a lack of crystal structure and also identify complex formation. IR can be used to differentiate between peaks that are sensitive to changes in crystallinity from those that are not. Residence time A high screw speed & powder flow rate reduce the mean residence time. Too high screw speed can result in insufficient exposure to heating zones & insufficient melting and/or dissolving of the drug substances as the residence time becomes too short. 15

16. Atomic force microscopy : AFM , a method which can study the surface microstructure of hot melt extrudate , can be used to visualize phase separation and/or non homogenicity of of HME samples. Raman Spectroscopy : To monitor the API concentration and the solid state of the formulation during HME. To identify interaction between drug and polymer based on peak shift in the spectra. To determine the residence time distribution. To study drug distribution in a matrix. 16

17. SOLID DISPERSION Solid dispersions is an approach to increase the solubility of the API and increase bioavailability. Eg : Lafutidine solid dispersion Amphiphilic Soluplus used as a primary solubilizing agent, with different concentrations of selected surfactants like PEG 400, Lutrol F127 (LF127 ), Lutrol F68 (LF68) were used to investigate their influence on formulations processing via HME. Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable 17

18. tablets Tablets of HME formulation can be formed by injection molding of the hot thermoplastic material or via milling of the cooled extrudate followed by mixing with excipient and tableting . A thermoplastic polymer is molten and injected into a specific mold. The molten polymer is solidified in the mold. A matrix tablet is then achieved. A tablet of desirable size and shape is easily obtained by injection-molding. Eg : Kaletra tablets 18

19. IMPLANTS By this method PLGA- or PLA- based implants are prepared. To fabricate PLGA or PLA implants, an operating temperature above their Tg has to be applied. By contrast, too high temperature is not allowed, because incorporating drugs can be thermally degraded. A drug, peptide or protein, which is sensitive to organic solvents or water, can be incorporated into the biodegradable implants. For example:1. Implanon , Nexplanon 2 .Haloperidol and Diclofenac sodium , have been loaded into the biodegradable implants by hot-melt extrusion the drug loading could be up to 40% 19

20. PELLETS Hot-melt extrusion is capable of preparing pellets with a compact structure that can resist rapid water penetration, thereby enabling the production of pellets with modified release. The extruded strands are transferred to a spheronizer where they are broken into short cylindrical rods and the ends are thereafter rounded off when in contact with the rotating friction plate. Pellets are usually filled into hard capsules to produce modified-release behaviour . 20

21. HME MARKETED PRODUCT 21

22. CONCLUSION Today melt granulation technology represents an efficient pathway for manufacture of various drug delivery systems. This technique is applicable to improve the dissolution characteristics of a poorly water-soluble drug by improving the dissolution rate and bioavailability of the drug by forming a solid dispersion or solid solution. Melt granulation technique is less time consuming and economic . 22

23. REFERENCES Dennis Douromis ,Hot melt extrusion:Pharmaceutical Application ,p:43-64. Halle Pradeep D;*, Sakhare Ram S;, Dadage Ketan K;, Birajdar Ganesh O; Raut Deepika B, A review on melt granulation technique,Journal of Pharmacy and Phytotherapeutics,p:6-10. Singhal S , Lohar V K, Arora V , Hot Melt Extrusion Technique,p :1-20. Pradip S Patel,  Jignesh  P  Raval ,  Hemul V. Patel, Review  on  the  pharmaceutical  applications  of hot melt extruder, Vol.3 Issue 2, April-June 2010  Michael M. Crowley and Feng Zhang, Pharmaceutical Applications of Hot-Melt Extrusion: Part I ,p:1-18. K.Kolter,M.Karl,A.Gryczke,Hot Melt Extrusion with BASF pharma polymers,p:15-37.   23

24. Hot melt extrusion,particle sciences drug development services,2011,vol3,p:1-2. Ankit patel , deepak sahu , ashok dashora , rahul garg , piyush agraval , a review of hot melt extrusion technique , international journal of innovative research in science, engineering and technology ,vol. 2, issue 6, june 2013 ,p:1-5. Ritesh fule , purnima amin,development and evaluation of lafutidine solid dispersion via hot melt extrusion, asian journal of pharmaceutical sciences 9 (2014), p:92-106. Malin lindén , hot-melt extrusion of modified release pellets ,p:6-12. Duangratana shuwisitkul , biodegradable implants with different drug release profiles,p:27-34 M.Karl,S.Nalawade,A,Maschke,Suitability of pure and plasticized polymers for HME,p:1-2. 24

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