A quality by design approach to develop topical creams via hot-melt extrusion technology

Mendonsa, Nicole; Pradhan, Adwait K.; Sharma, Pravin Kumar; Prado, Rosa Maria Badani; Murthy, S. Narasimha; Kundu, Santanu; Repka, Michael A.

doi:10.1016/j.ejps.2019.06.002

Cited by 22 publications

(22 citation statements)

References 35 publications

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“…Pertaining to DoE formulations, this trend was observed for a low viscous formulation (F 15 ) presenting the best c 1 , as well as, R 24h results. However, more viscous systems also presented elevated results for drug release [85]. This unexpected behavior can be ascribed to smaller droplet sizes and particular rheological aspects, such as a thixotropic behavior and viscoelastic properties.…”

Section: Product Performance Ivrtmentioning

confidence: 94%

Progressing Towards the Sustainable Development of Cream Formulations

2020

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This work aims at providing the assumptions to assist the sustainable development of cream formulations. Specifically, it envisions to rationalize and predict the effect of formulation and process variability on a 1% hydrocortisone cream quality profile, interplaying microstructure properties with product performance and stability. This tripartite analysis was supported by a Quality by Design approach, considering a three-factor, three-level Box–Behnken design. Critical material attributes and process parameters were identified from a failure mode, effects, and criticality analysis. The impact of glycerol monostearate amount, isopropyl myristate amount, and homogenization rate on relevant quality attributes was estimated crosswise. The significant variability in product droplet size, viscosity, thixotropic behavior, and viscoelastic properties demonstrated a noteworthy influence on hydrocortisone release profile (112±2-196±7 μg/cm2/√h) and permeation behavior (0.16±0.03-0.97±0.08 μg/cm2/h), and on the assay, instability index and creaming rate, with values ranging from 81.9 to 120.5%, 0.031±0.012 to 0.28±0.13 and from 0.009±0.000 to 0.38±0.07 μm/s, respectively. The release patterns were not straightforwardly correlated with the permeation behavior. Monitoring the microstructural parameters, through the balanced adjustment of formulation and process variables, is herein highlighted as the key enabler to predict cream performance and stability. Finally, based on quality targets and response constraints, optimal working conditions were successfully attained through the establishment of a design space.

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Section: Product Performance Ivrtmentioning

confidence: 94%

Progressing Towards the Sustainable Development of Cream Formulations

2020

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“…The attraction forces within fluids that establish the degree of viscosity are sensitive toward changes in temperature [130]. Additionally, some systems can portray reversible or irreversible structural changes induced by the flow of fluids [131]. Flow behaviour is classified as either Newtonian or non-Newtonian [132].…”

Section: Viscositymentioning

confidence: 99%

Development of Topical/Transdermal Self-Emulsifying Drug Delivery Systems, Not as Simple as Expected

2020

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Self-emulsifying drug delivery systems (SEDDSs) originated as an oral lipid-based drug delivery system with the sole purpose of improving delivery of highly lipophilic drugs. However, the revolutionary drug delivery possibilities presented by these uniquely simplified systems in terms of muco-adhesiveness and zeta-potential changing capacity lead the way forward to ground-breaking research. Contrarily, SEDDSs destined for topical/transdermal drug delivery have received limited attention. Therefore, this review is focused at utilising principles, established during development of oral SEDDSs, and tailoring them to fit evaluation strategies for an optimised topical/transdermal drug delivery vehicle. This includes a detailed discussion of how the authentic pseudo-ternary phase diagram is employed to predict phase behaviour to find the self-emulsification region most suitable for formulating topical/transdermal SEDDSs. Additionally, special attention is given to the manner of characterising oral SEDDSs compared to topical/transdermal SEDDSs, since absorption within the gastrointestinal tract and the multi-layered nature of the skin are two completely diverse drug delivery territories. Despite the advantages of the topical/transdermal drug administration route, certain challenges such as the relatively undiscovered field of skin metabolomics as well as the obstacles of choosing excipients wisely to establish skin penetration enhancement might prevail. Therefore, development of topical/transdermal SEDDSs might be more complicated than expected.

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“…Scientists may opt for a variety of die shapes and sizes. For example, flat dies are used for the production of films [33,46,47] and patches [48], whereas circular dies are used for pelletization and spheronization [29,49,50]. The molten drug-polymer mixture can also be filled into molds using injection molding.…”

Section: Downstream Processing-severalmentioning

confidence: 99%

“…For instance, these molds can be formed to yield the tablet, capsule shapes, ear inserts, or pediatric formulations [26,51]. Some of the dosage forms that have been previously studied include rods, films [33], spherical pellets [29,50], punched and injection molded tablets [52][53][54], and granules [54,55].…”

Section: Downstream Processing-severalmentioning

confidence: 99%

Manufacturing strategies to develop amorphous solid dispersions: An overview

Mendonsa

Almutairy

Kallakunta

et al. 2020

Journal of Drug Delivery Science and Technology

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Since the past several decades, poor water solubility of existing and new drugs in the pipeline have remained a challenging issue for the pharmaceutical industry. Literature describes several approaches to improve the overall solubility, dissolution rate, and bioavailability of drugs with poor water solubility. Moreover, the development of amorphous solid dispersion (SD) using suitable polymers and methods have gained considerable importance in the recent past. In the present review, we attempt to discuss the important and industrially scalable thermal strategies for the development of amorphous SD. These include both solvent (spray drying and fluid bed processing) and fusion (hot melt extrusion and KinetiSol®) based techniques. The current review also provides insights into the thermodynamic properties of drugs, their polymer miscibility and solubility, and their molecular dynamics to develop stable and more efficient amorphous SD.

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A quality by design approach to develop topical creams via hot-melt extrusion technology

Cited by 22 publications

References 35 publications

Progressing Towards the Sustainable Development of Cream Formulations

Progressing Towards the Sustainable Development of Cream Formulations

Development of Topical/Transdermal Self-Emulsifying Drug Delivery Systems, Not as Simple as Expected

Manufacturing strategies to develop amorphous solid dispersions: An overview

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