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. 2023 Sep 1;15(9):2267.
doi: 10.3390/pharmaceutics15092267.

Twin Screw Melt Granulation: A Single Step Approach for Developing Self-Emulsifying Drug Delivery System for Lipophilic Drugs

Dinesh Nyavanandi  1 , Preethi Mandati  1 , Sagar Narala  1 , Abdullah Alzahrani  1 , Praveen Kolimi  1 , Sateesh Kumar Vemula  1 , Michael A Repka  1   2
Affiliations

Twin Screw Melt Granulation: A Single Step Approach for Developing Self-Emulsifying Drug Delivery System for Lipophilic Drugs

Dinesh Nyavanandi et al. Pharmaceutics. .

Abstract

The current research aims to improve the solubility of the poorly soluble drug, i.e., ibuprofen, by developing self-emulsifying drug delivery systems (SEDDS) utilizing a twin screw melt granulation (TSMG) approach. Gelucire® 44/14, Gelucire® 48/16, and Transcutol® HP were screened as suitable excipients for developing the SEDDS formulations. Initially, liquid SEDDS (L-SEDDS) were developed with oil concentrations between 20-50% w/w and surfactant to co-surfactant ratios of 2:1, 4:1, 6:1. The stable formulations of L-SEDDS were transformed into solid SEDDS (S-SEDDS) using a suitable adsorbent carrier and compressed into tablets (T-SEDDS). The S-SEDDS has improved flow, drug release profiles, and permeability compared to pure drugs. The existence of the drug in an amorphous state was confirmed by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis (PXRD). The formulations with 20% w/w and 30% w/w of oil concentration and a 4:1 ratio of surfactant to co-surfactant have resulted in a stable homogeneous emulsion with a globule size of 14.67 ± 0.23 nm and 18.54 ± 0.55 nm. The compressed tablets were found stable after six months of storage at accelerated and long-term conditions. This shows the suitability of the TSMG approach as a single-step continuous manufacturing process for developing S-SEDDS formulations.

Keywords: globule size; liquid SEDDS; polydispersity index; self-emulsifying drug delivery system; solid SEDDS; twin screw melt granulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Solubility of the drug (ibuprofen) in various lipid excipients. The solubility is represented as the amount of drug dissolved in one gram of lipid.
Figure 2
Figure 2
Ternary phase diagram representing emulsification region (black box) among the investigated concentrations. The green circled points represent the stable formulation after 48 h of storage at ambient temperature.
Figure 3
Figure 3
Thermal properties of pure drug, physical mixtures, pure excipients, and granules of S1 and S2 formulations.
Figure 4
Figure 4
Hot-stage microscopy representing the solubilizing capacity of the lipid excipients. S1 and S2 represents the granule formulations.
Figure 5
Figure 5
PXRD diffractograms of pure drug, Neusilin® US2, Gelucire® 44/14, Gelucire® 48/16, and granules of S-SEDDS formulations (S1 & S2).
Figure 6
Figure 6
FTIR spectra of pure drug, Neusilin® US2, Gelucire® 44/14, Gelucire® 48/16, and granules of S-SEDDS formulations (S1 & S2) (X-axis: wavenumber; Y-axis: absorbance).
Figure 7
Figure 7
Scanning electron microscopy analysis for the (A) pure active substance, Ibuprofen (×200 magnification) (B) pure solid adsorbent carrier Neusilin® US2 (×300 magnification) (C) granules of S-SEDDS; S1 (×180 magnification) (D) granules of S-SEDDS; S2 (×650 magnification).
Figure 8
Figure 8
TEM images of S-SEDDS formulations (S1, S2). (A) Formulation S1 (B) Formulation S2.
Figure 9
Figure 9
In vitro drug release profiles of S - SEDDS granules in (A) water, (B) 0.1N HCl, and (C) pH 7.2 phosphate buffer solution (PBS).
Figure 10
Figure 10
In vitro diffusion studies of S-SEDDS formulations (S1, S2) in comparison with pure drug.
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References

    1. Kumar S., Dilbaghi N., Saharan R., Bhanjana G. Nanotechnology as Emerging Tool for Enhancing Solubility of Poorly Water-Soluble Drugs. Bionanoscience. 2012;2:227–250. doi: 10.1007/s12668-012-0060-7. - DOI
    1. Khan K.U., Minhas M.U., Badshah S.F., Suhail M., Ahmad A., Ijaz S. Overview of Nanoparticulate Strategies for Solubility Enhancement of Poorly Soluble Drugs. Life Sci. 2022;291:120301. doi: 10.1016/j.lfs.2022.120301. - DOI - PubMed
    1. Koehl N.J., Henze L.J., Holm R., Kuentz M., Keating J.J., de Vijlder T., Marx A., Griffin B.T. Lipophilic Salts and Lipid-Based Formulations for Bridging the Food Effect Gap of Venetoclax. J. Pharm. Sci. 2022;111:164–174. doi: 10.1016/j.xphs.2021.09.008. - DOI - PubMed
    1. Teżyk M., Milanowski B., Ernst A., Lulek J. Recent Progress in Continuous and Semi-Continuous Processing of Solid Oral Dosage Forms: A Review. Drug Dev. Ind. Pharm. 2015;42:1195–1214. doi: 10.3109/03639045.2015.1122607. - DOI - PubMed
    1. Sohail Arshad M., Zafar S., Yousef B., Alyassin Y., Ali R., AlAsiri A., Chang M.W., Ahmad Z., Ali Elkordy A., Faheem A., et al. A Review of Emerging Technologies Enabling Improved Solid Oral Dosage Form Manufacturing and Processing. Adv. Drug Deliv. Rev. 2021;178:113840. doi: 10.1016/j.addr.2021.113840. - DOI - PubMed