Systematic screening of pharmaceutical polymers for hot melt extrusion processing: a comprehensive review

Thakkar, Rishi; Thakkar, Ruchi; Pillai, Amit Raviraj; Ashour, Eman A.; Repka, Michael A.

doi:10.1016/j.ijpharm.2019.118989

Cited by 103 publications

(60 citation statements)

References 103 publications

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“…Based on the thermal events observed during the screening process, the processing temperature for the manufacturing of the ASDs was set to 130 °C. After evaluating the compatibility of drug-polymer miscibility by applying theoretical structural orientation based prediction model of Hansen Solubility Parameters (∆δ = 4.11 MPa 0.5 i.e., <7) [ 23 ] of ibuprofen (δ t = 19.89 MPa 0.5 ) [ 37 ] and HPMC-AS polymers (δ t = 24 MPa 0.5 ) [ 38 ], it was confirmed that the drug-polymer pairs were highly likely to be miscible and thus form a solid-dispersion. The theoretical evaluation of miscibility before manufacturing ASDs is crucial to predict the possibility of a crystalline drug to convert into its amorphous counterpart by balancing the energy required for intramolecular interaction within a drug to that of intermolecular interaction between that drug and a carrier matrix such as a polymer [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

“…As observed in a study by Ewing and colleagues (2014) with indomethacin and HPMC, it was capable to prevent recrystallization of indomethacin on storage and did not hinder the release of indomethacin during the in vitro testing as its interaction with the dissolution media were considered to be stronger as compared to the weak interactions it has with the drug, thereby releasing the drug in the medium [ 48 ]. Although there have been cases reported with other drug-polymer pairs such as polyethylene glycol and indomethacin, where the drug recrystallizes during the storage and release testing, which is attributed to the solubilization capacity of the polymer and the compatibility of the drug and the polymer [ 23 ]. In our case, as per the theoretical parameters discussed previously the drug and the polymer are compatible with one another, which is also supported by the solid-state characterizations conducted during the study.…”

Section: Resultsmentioning

confidence: 99%

“…Amongst the aforementioned platforms, only FDM allows the use of hot-melt extrusion (HME) based filaments which are known for their capabilities of solubility enhancement, specifically for BCS class II drugs [ 16 , 17 ], which makes it a preferred platform for drugs with poor water solubility over the other techniques. Moreover, FDM is known to have the most versatility in terms of designing 3-D structures [ 18 , 19 , 20 ] and the available pharmaceutical polymers compatible with the process [ 20 , 21 , 22 , 23 ]. It has been recognized that FDM has the most immediate potential for unit dose fabrication as it uses polymeric filaments which could be customized or tuned to the specific needs of the printed products.…”

Section: Introductionmentioning

confidence: 99%

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Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

et al. 2020

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This research demonstrates the use of fill density as an effective tool for controlling the drug release without changing the formulation composition. The merger of hot-melt extrusion (HME) with fused deposition modeling (FDM)-based 3-dimensional (3-D) printing processes over the last decade has directed pharmaceutical research towards the possibility of printing personalized medication. One key aspect of printing patient-specific dosage forms is controlling the release dynamics based on the patient’s needs. The purpose of this research was to understand the impact of fill density and interrelate it with the release of a poorly water-soluble, weakly acidic, active pharmaceutical ingredient (API) from a hydroxypropyl methylcellulose acetate succinate (HPMC-AS) matrix, both mathematically and experimentally. Amorphous solid dispersions (ASDs) of ibuprofen with three grades of AquaSolveTM HPMC-AS (HG, MG, and LG) were developed using an HME process and evaluated using solid-state characterization techniques. Differential scanning calorimetry (DSC), powder X-ray diffraction (pXRD), and polarized light microscopy (PLM) confirmed the amorphous state of the drug in both polymeric filaments and 3D printed tablets. The suitability of the manufactured filaments for FDM processes was investigated using texture analysis (TA) which showed robust mechanical properties of the developed filament compositions. Using FDM, tablets with different fill densities (20–80%) and identical dimensions were printed for each polymer. In vitro pH shift dissolution studies revealed that the fill density has a significant impact (F(11, 24) = 15,271.147, p < 0.0001) and a strong negative correlation (r > −0.99; p < 0.0001) with the release performance, where 20% infill demonstrated the fastest and most complete release, whereas 80% infill depicted a more controlled release. The results obtained from this research can be used to develop a robust formulation strategy to control the drug release from 3D printed dosage forms as a function of fill density.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

et al. 2020

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“…Compared with traditional methods, HME is a simpler process to continuously prepare sustained-release tablets. Recently, this technique has been employed to obtain floating GRDDS (Table 8) using insoluble polymers as matrix forming agents, mixed with a soluble polymer to facilitate water penetration in order to form a gel-like material to control the drug release [147]. Some specific components of the formulations, such as stearic acid [60,148] and stearyl alcohol [149] are necessary as a processing aid for HME.…”

Section: Multi-unit Grdds Developed By Hot Melt Extrusion (Hme) and 3mentioning

confidence: 99%

In-Depth Study into Polymeric Materials in Low-Density Gastroretentive Formulations

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The extensive use of oral dosage forms for the treatment of diseases may be linked to deficient pharmacokinetic properties. In some cases the drug is barely soluble; in others, the rapid transit of the formulation through the gastrointestinal tract (GIT) makes it difficult to achieve therapeutic levels in the organism; moreover, some drugs must act locally due to a gastric pathology, but the time they remain in the stomach is short. The use of formulations capable of improving all these parameters, as well as increasing the resident time in the stomach, has been the target of numerous research works, with low-density systems being the most promising and widely explored, however, there is further scope to improve these systems. There are a vast variety of polymeric materials used in low-density gastroretentive systems and a number of methods to improve the bioavailability of the drugs. This works aims to expedite the development of breakthrough approaches by providing an in-depth understanding of the polymeric materials currently used, both natural and synthetic, their properties, advantages, and drawbacks.

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“…Hot melt extrusion (HME) is a continuous pharmaceutical process that has recently attracted considerable attention [19] for developing formulations of poorly soluble drugs [20], its applicability to an increasing range of materials [21] and its solvent-free process [22]. Yet, HME requires a time-consuming and labour-intensive conventional cleaning procedure [22], particularly after a change of formulation [3].…”

Section: Introductionmentioning

confidence: 99%

Novel Cleaning-in-Place Strategies for Pharmaceutical Hot Melt Extrusion

et al. 2020

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To avoid any type of cross-contamination, residue-free production equipment is of utmost importance in the pharmaceutical industry. The equipment cleaning for continuous processes such as hot melt extrusion (HME), which has recently gained popularity in pharmaceutical applications, necessitates extensive manual labour and costs. The present work tackles the HME cleaning issue by investigating two cleaning strategies following the extrusion of polymeric formulations of a hormonal drug and for a sustained release formulation of a poorly soluble drug. First, an in-line quantification by means of UV–Vis spectroscopy was successfully implemented to assess very low active pharmaceutical ingredient (API) concentrations in the extrudates during a cleaning procedure for the first time. Secondly, a novel in-situ solvent-based cleaning approach was developed and its usability was evaluated and compared to a polymer-based cleaning sequence. Comparing the in-line data to typical swab and rinse tests of the process equipment indicated that inaccessible parts of the equipment were still contaminated after the polymer-based cleaning procedure, although no API was detected in the extrudate. Nevertheless, the novel solvent-based cleaning approach proved to be suitable for removing API residue from the majority of problematic equipment parts and can potentially enable a full API cleaning-in-place of a pharmaceutical extruder for the first time.

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Systematic screening of pharmaceutical polymers for hot melt extrusion processing: a comprehensive review

Cited by 103 publications

References 103 publications

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

Novel On-Demand 3-Dimensional (3-D) Printed Tablets Using Fill Density as an Effective Release-Controlling Tool

In-Depth Study into Polymeric Materials in Low-Density Gastroretentive Formulations

Novel Cleaning-in-Place Strategies for Pharmaceutical Hot Melt Extrusion

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