Comparison of HPMC based polymers performance as carriers for manufacture of solid dispersions using the melt extruder

Ghosh, Indrajit; Snyder, James V.; Vippagunta, Radha; Alvine, Marilyn; Vakil, Ronak; Tong, Wei-Qin; Vippagunta, Sudha R.

doi:10.1016/j.ijpharm.2011.05.073

Cited by 75 publications

(35 citation statements)

References 23 publications

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“…It is worth noting that as these windows are defined for neat polymers, many polymers that exhibit viscosities just above the defined maximum viscosity limit will be sufficiently plasticized with the addition of API to bring down the viscosity to extrudable levels. For example, low molecular weight grades of HPMC and HPMC AS have been extensively investigated by hot-melt extrusion in ASDs (57,(59)(60)(61). Additionally, the complex viscosity range was correlated to the torque limitation for a small-scale extruder, and higher torque capacity will often be achievable in larger scale extruders.…”

Section: Discussionmentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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Abstract. Thermal processing of amorphous solid dispersions continues to gain interest in the pharmaceutical industry, as evident by several recently approved commercial products. Still, a number of pharmaceutical polymer carriers exhibit thermal or viscoelastic limitations in thermal processing, especially at smaller scales. Additionally, active pharmaceutical ingredients with high melting points and/or that are thermally labile present their own specific challenges. This review will outline a number of formulation and process-driven strategies to enable thermal processing of challenging compositions. These include the use of traditional plasticizers and surfactants, temporary plasticizers utilizing sub-or supercritical carbon dioxide, designer polymers tailored for hot-melt extrusion processing, and KinetiSol® Dispersing technology. Recent case studies of each strategy will be described along with potential benefits and limitations.

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Section: Discussionmentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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“…The rheological and thermal properties of cellulosic polymers were recently investigated, with no extrudable temperature range of neat HPMC E (6cps) below its degradation temperature identified due to the high viscosity of the polymer (52). Extrusion with HPMC has been previously conducted with the low viscosity grades available (19,47,53) and often still incorporates the use of a plasticizer to reduce processing temperature. Extrusion experiments with higher molecular weight grades of HPMC have been studied and consistently yield high torque loads and significant browning (28,51).…”

Section: Discussionmentioning

confidence: 99%

“…Processing of APIs that have high melting points or are thermally labile continues to be a challenge due to energy input required during HME to produce an amorphous final product (17,18). Additionally, higher molecular weight polymers that may be effective for stabilizing the amorphous drug may be too viscous for processing via HME due to high torque loads, requiring the use of plasticizers that decrease the final product glass transition temperature (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions

et al. 2015

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Abstract. Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.

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“…Furthermore, low or insufficient concentration of stabilizer will cause instability and recrystallization. TPGS has been shown to improve the bioavailability of many compounds [36]. The combination of TPGS and HPMC in the nanosuspension formulation was shown to inhibit the crystal growth within the system [37].…”

Section: Particle Size Analysis and Polydispersity Index Measurementmentioning

confidence: 99%

Formulation and Evaluation of Polymeric Nanosuspension of Naringenin

Sumathi¹,

Sengodan²,

Sivakumar³

2017

Int J App Pharm

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, S. TAMIZHARASI, T. SIVAKUMAR Nandha College of Pharmacy and Research Institute, Erode 630052, Tamilnadu, IndiaEmail: sumoraji@gmail.comObjective: The objective of this study was to formulate and evaluate the poorly soluble drug, naringenin (NAR) into nanosuspension to increase the solubility and enhance the dissolution rate and then improve its bioavailability.Methods: Nanosuspenion of naringenin (NARNS) was prepared using high-pressure homogenization method using Soya lecithin, Polaxamer-407, Polaxamer-188, Hydroxypropyl methyl cellulose (HPMC) and Tween-80. Ten formulations were prepared to show the effect of stabilizer and its ratio. D-α-Tocopheryl polyethene glycol succinate 1000 (TPGS) was added as a co-stabilizer. All these formulations were evaluated for their particle size, PDI, zeta potential, FT-IR study, drug content, saturation solubility studies, entrapment efficiency, in vitro permeability and in vitro drug release. The formulation was further evaluated for scanning electron microscope (SEM), differential scanning calorimetry (DSC) and Powder X-ray diffraction (P-XRD) and hemocompatibility assessment.Results: All the prepared formulations were in the nano size. The optimum concentration of the stabilizer was in the formulation was found 1:1.5:1 (drug: stabilizer: co-stabilizer ratio). Dramatic effect of the particle size reduction was found by the addition of the co-stabilizer (TPGS) in formulation N2 that has P. S 80.52±0.13 nm. The solubility and dissolution of NAR in the form of NARNS were significantly higher than those of pure NAR. SEM report shows that naringenin nanosuspension revealed a smooth texture. P-XRD crystallography diffraction and DSC studies indicated that the crystalline state of NAR was converted into amorphous nature. The safety evaluation showed that NARNS provided a lower rate of erythrocyte hemolysis.Keywords: Naringenin, High-Pressure Homogenization, Nanosuspenion, Solubility, Bioavailability Conclusion:In this study, (NARNS) was successfully carried out by high-pressure homogenization technique and characterized. The physiochemical characterization shown that crystalline naringenin was converted to a polymorphic form (DSC and P-XRD Study) which evidenced by enhanced dissolution rate in comparisons of the formulation with (NAR) pure drug. The NARNS has shown 7.5±0.4 fold increased relative bioavailability when compared to the NAR. The increased drug dissolution rate may have a significant impact in absorption which in turn the improved oral bioavailability of naringenin. Thus, this delivery system may prefer to improve the dissolution of poorly soluble drugs like NAR and thus enhanced oral bioavailability. The safety evaluation showed that nanoformulation (NF2) shows a lower rate of erythrocyte hemolysis. These findings suggest that the selected formulation may represent a promising new drug formulation for intravenous administration in the treatment of certain cancers.

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Comparison of HPMC based polymers performance as carriers for manufacture of solid dispersions using the melt extruder

Cited by 75 publications

References 23 publications

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions

Formulation and Evaluation of Polymeric Nanosuspension of Naringenin

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