A Comparison Between Lab-Scale and Hot-Melt-Extruder-Based Anti-inflammatory Ointment Manufacturing

Thakkar, Rishi; Ashour, Eman A.; Shukla, Ashay; Wang, Rui; Chambliss, Walter G.; Bandari, Suresh; Murthy, Narasimha; Repka, Michael A.

doi:10.1208/s12249-020-01738-5

Cited by 15 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The acid functional group in the drug has the most potential to interact with other molecules due to the partial negative charge on the oxygen atom. It also plays a crucial role in recrystallization [ 45 ]. The FT–IR spectrum shows a peak shift towards a higher wavenumber which may be due to the interaction of the acid functional group with the polymer, which may contribute towards stabilizing the ASDs [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Resultsmentioning

confidence: 99%

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

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…One indicator is the disappearance or reduced intensity of functional 'stretch' peaks as observed for 'OeH' and the 'NeH' peaks (i.e., visible in the pure drug and physical mixtures but absent in the ASDs manufactured using both SLS and HME). 45 Another noticeable change is the peak shifts which usually represent a change in confirmation/steric environment as seen for the 'CeO' stretch peaks of RTV shifting to a lower wavenumber in the ASDs. 46 Finally, the formation of hybrid peaks represents the mixing of two components at a molecular level, which is expected in an ASD and can be observed by the hybrid complex formed in the ASDs at 1667 cm À1 (shift from 1612 cm À1 , 1662 cm À1 for the drug and 1681 cm À1 for the polymer) and 1735 cm À1 (shift from 1704 cm À1 for the drug and 1740 cm À1 for the polymer) which represent the carbonyl and ester groups, whereas these peaks, although superimposed, are distinct in the physical mixtures tested.…”

Section: Asd Tablet Characterizationmentioning

confidence: 99%

Selective Laser Sintering 3-Dimensional Printing as a Single Step Process to Prepare Amorphous Solid Dispersion Dosage Forms for Improved Solubility and Dissolution Rate

Davis

Thakkar

et al. 2021

Journal of Pharmaceutical Sciences

Self Cite

View full text Add to dashboard Cite

This study reports the development of ritonavir-copovidone amorphous solid dispersions (ASDs) and dosage forms thereof using selective laser sintering (SLS) 3-dimensional (3-D) printing in a single step, circumventing the post-processing steps required in common techniques employed to make ASDs. For this study, different drug loads of ritonavir with copovidone were processed at varying processing conditions to understand the impact, range, and correlation of these parameters for successful ASD formation. Further, ASDs characterized using conventional and advanced solid-state techniques including wide-angle X-ray scattering (WAXS), solid-state nuclear magnetic resonance (ssNMR), revealed the full conversion of the crystalline drug to its amorphous form as a function of laser-assisted selective fusion in a layer-by-layer manner. It was observed that an optimum combination of the powder flow properties, surface temperature, chamber temperature, laser speed, and hatch spacing was crucial for successful ASD formation, any deviations resulted in print failures or only partial amorphous conversion. Moreover, a 21fold increase in solubility was demonstrated by the SLS 3-D printed tablets. The results confirmed that SLS 3-D printing can be used as a single-step platform for creating ASD-based pharmaceutical dosage forms with a solubility advantage.

show abstract

“…For this, all the 3 formulations were stored in a stability chamber for 3 months. e condition of stability chamber was 40 °C ± 2 °C/75% RH ± 5% RH [26]. e samples were evaluated for ketoconazole assay, pH change, smoothness, and color change at the end of first and third month.…”

Section: Determination Of the Active Ingredient In The Formulationmentioning

confidence: 99%

Physicochemical Evaluation of Diploknema butyracea Seed Extract and Formulation of Ketoconazole Ointment by Using the Fat as a Base

Pandey

Khanal

Bhandari

et al. 2021

Journal of Food Quality

View full text Add to dashboard Cite

The fat obtained from the ripened seeds of Diploknema butyracea is widely used as a vegetable oil in rural areas of Nepal. This study was aimed for the physicochemical evaluation (acid value, iodine value, saponification value, peroxide value, ester value, pH, and liquefaction point) of the Diploknema butyracea seed extract (chyuri fat) and the formulation of 2% w/w ketoconazole ointment by using it as a base. All the physicochemical parameters were determined quantitatively by using the method of Indian Pharmacopoeia (IP), volume-I. By fusion method, 3 different formulations F-A, F-B, and F-C were prepared, in which different proportions of chyuri fat, polyethylene glycol 6000 (PEG 600), Tween 80, and propylene glycol were used as an ointment base. Various quality parameters such as spreadability, extrudability, viscosity, smoothness, pH, average fill weight, assay, content uniformity, accelerated stability, and drug release profiles were determined. HPLC was used for the determination of ketoconazole content in the ointment formulations. Physicochemical evaluation of the chyuri fat ensured its suitability for industrial purpose. The active ingredient release profile of formulations F-A (87.71%), F-B (88.89%), and F-C (91.09%) after 5 hours were within acceptable range along with other parameters. Assay of the formulations F-A, F-B, and F-C were reported to be 103.01, 107.9, and 102.45%, respectively. Overall, evaluation of the formulation F-A, prepared by using chyrui fat only, gave satisfactory results and most of the parameters were statistically similar ( p > 0.05 ) to the F-B and F-C formulated by incorporating a certain proportion of synthetic base. Thus it can be concluded that chyuri fat can be the best alternative to replace the expensive synthetic base.

show abstract

A Comparison Between Lab-Scale and Hot-Melt-Extruder-Based Anti-inflammatory Ointment Manufacturing

Cited by 15 publications

References 32 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

Selective Laser Sintering 3-Dimensional Printing as a Single Step Process to Prepare Amorphous Solid Dispersion Dosage Forms for Improved Solubility and Dissolution Rate

Physicochemical Evaluation of Diploknema butyracea Seed Extract and Formulation of Ketoconazole Ointment by Using the Fat as a Base

Contact Info

Product

Resources

About