Improving the wetting and dissolution of ibuprofen using solventless co-milling

Varghese, Sophia; Ghoroi, Chinmay

doi:10.1016/j.ijpharm.2017.09.062

Cited by 28 publications

(5 citation statements)

References 31 publications

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“…Milling and co-milling are well known techniques in the pharmaceutical industry, having a positive influence on the kinetic solubility and dissolution rate of sparingly soluble drugs [ 74 , 75 , 76 ]. The milling of drug reduces the drug particles to the micron or submicron level and provides a larger surface area, which results in the improvement of wettability and dissolution [ 77 , 78 , 79 ]. However, the milling of powder also generates certain shortcomings, e.g., the coarser particles are turned into finer ones that are more energetic and therefore result in a higher surface energy.…”

Section: Hpmc (Hydroxypropyl Methylcellulose)mentioning

confidence: 99%

“…This increases the interactions among particles, increases their cohesiveness, and increases the aggregate size, which contributes to poor dissolution [ 53 , 80 ]. In order to overcome these disadvantages and improve the milling efficiency, a favorable technique by co-milling with appropriate surface modifiers was successfully applied [ 77 , 79 , 81 , 82 ]. Co-milling or co-grinding of drugs with various surface modifiers, such as lactose, MCC, starch, PVP, HPMC, etc.…”

Section: Hpmc (Hydroxypropyl Methylcellulose)mentioning

confidence: 99%

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Surface Modifiers on Composite Particles for Direct Compaction

Chen

Liu²,

Zhu³

et al. 2022

Pharmaceutics

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Direct compaction (DC) is considered to be the most effective method of tablet production. However, only a small number of the active pharmaceutical ingredients (APIs) can be successfully manufactured into tablets using DC since most APIs lack adequate functional properties to meet DC requirements. The use of suitable modifiers and appropriate co-processing technologies can provide a promising approach for the preparation of composite particles with high functional properties. The purpose of this review is to provide an overview and classification of different modifiers and their multiple combinations that may improve API tableting properties or prepare composite excipients with appropriate co-processed technology, as well as discuss the corresponding modification mechanism. Moreover, it provides solutions for selecting appropriate modifiers and co-processing technologies to prepare composite particles with improved properties.

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Section: Hpmc (Hydroxypropyl Methylcellulose)mentioning

confidence: 99%

Section: Hpmc (Hydroxypropyl Methylcellulose)mentioning

confidence: 99%

Surface Modifiers on Composite Particles for Direct Compaction

Chen

Liu²,

Zhu³

et al. 2022

Pharmaceutics

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“…All k values for MLX samples prepared by co-milling (CM-) are greater than those for the mixture prepared by blending micronized MLX with SLS (R10-15/10 in Table 3 ), with p -values based on the t -test range of 0.001–0.047, demonstrating that co-milling is effective in terms of improving the dissolution properties of MLX through various mechanisms. During the process of co-milling MLX with SLS, the following phenomena were observed: an ordered mixture in which the MLX is in close contact with the SLS [ 28 ], hydrophilization of the MLX surface by increasing the polar surface energy component of the MLX particles because they can interact with weak secondary bonds [ 29 ], an increase the wettability of MLX particles by SLS [ 21 ], an increase the specific surface area of the particles, and an increase in the angularity of the particles [ 4 ]. The crystallinity of the investigated samples did not differ significantly, as confirmed by XRD measurements ( Figure 4 a); a decrease in the intensity (count) of diffracted signals of MLX was not visible.…”

Section: Resultsmentioning

confidence: 99%

Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate

2022

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Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5–25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion—surface utilization factor—were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing.

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“…HPMC and HPMCAS form H-bonds by offering protons and have been found to produce solid dispersions with improved drug solubility [19]. MCC has H-bond donors and has been found to increase ibuprofen solubility and dissolution by co-milling with the drug [27]. PVP has proton accepting carbonyl group and less strong accepting N atom and can act both as solubilizer and crystallization inhibitor [28].…”

Section: Resultsmentioning

confidence: 99%

Solubility Improvement of Progesterone from Solid Dispersions Prepared by Solvent Evaporation and Co-milling

et al. 2020

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The aim of this contribution was to evaluate the impact of processing methods and polymeric carriers on the physicochemical properties of solid dispersions of the poorly soluble drug progesterone (PG). Five polymers: hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP) and silica (SiO2), and two processing methods: solvent evaporation (SE) and mechano-chemical activation by co-milling (BM) were applied. H-bonding was demonstrated by FTIR spectra as clear shifting of drug peaks at 1707 cm−1 (C20 carbonyl) and 1668 cm−1 (C3 carbonyl). Additionally, spectroscopic and thermal analysis revealed the presence of unstable PG II polymorphic form and a second heating DSC cycle, the presence of another polymorph possibly assigned to form III, but their influence on drug solubility was not apparent. Except for PG–MCC, solid dispersions improved drug solubility compared to physical mixtures. For SE dispersions, an inverse relationship was found between drug water solubility and drug–polymer Hansen solubility parameter difference (Δδt), whereas for BM dispersions, the solubility was influenced by both the intermolecular interactions and the polymer Tg. Solubility improvement with SE was demonstrated for all except PG–MCC dispersions, whereas improvement with BM was demonstrated by the PG–HPMC, PG–PVP and PG–HPMCAS dispersions, the last showing impressive increase from 34.21 to 82.13 μg/mL. The extensive H-bonding between PG and HPMCAS was proved by FTIR analysis of the dispersion in the liquid state. In conclusion, although SE improved drug solubility, BM gave more than twice greater improvement. This indicates that directly operating intermolecular forces are more efficient than the solvent mediated.

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Improving the wetting and dissolution of ibuprofen using solventless co-milling

Cited by 28 publications

References 31 publications

Surface Modifiers on Composite Particles for Direct Compaction

Surface Modifiers on Composite Particles for Direct Compaction

Dissolution Kinetics of Meloxicam Formulations Co-Milled with Sodium Lauryl Sulfate

Solubility Improvement of Progesterone from Solid Dispersions Prepared by Solvent Evaporation and Co-milling

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