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Hi, I have a question regarding my university assignment. In this case; it’s medroxyprogesterone. We all know that it’s a hydrophobic drug, hence, we are assigned to create a sterile injection in aqueous formulation. Aqueous means it has to be solubilized in water, but, the problem here is, medroxyprogesterone is poorly-water soluble but is really soluble in chloroform. So, I just wanna discuss about it here. How do we make it to be soluble in water (is it possible to do it so?) Thank you. And the questions below (the handwritten ones) I hope you can explain that also, theyre the things we have to present.. Help me, thank you!

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    $\begingroup$ That's a broad question. But under merckmanuals.com/professional/appendixes/… you find an entry about this drug in general, and a subsection about dosage forms which mentions some of the carriers teaming up for such a more lipophilic than hydrophilic molecule: methylparaben, polyethylene glycol, propylparaben. If your API tends to form easily crystals with acids or bases, then formulation as co-crystals may alter the both the cinetics as well as thermodynamic solubility parameters quite a lot. $\endgroup$ – Buttonwood Oct 31 at 21:37
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Medroxyprogesterone is a steroid. However, active drug is its acetate form, medroxyprogesterone acetate, which is sold under the brand name Depo-Provera among others (Wikipedia). Nonetheless, either is hydrophobic, and hence, should have prepared suitable way for administration to have better bio-availability. One of these methods are liposomal preparation (Ref.1). An easy loposormal preparation of a steroidal drug is summarized as follows (Ref.2):

The standard liposome formulation was prepared under aseptic conditions: Dipalmitoyl phosphatidylcholine ($\pu{6 mg}$), egg yolk phosphatidic acid ($\pu{1 mg}$), and cortisol palmitate ($\pu{3 mg}$) were dissolved in chloroform ($\pu{1.25 mL}$). This solution was rotary evaporated to dryness in vacuo at $\pu{55 ^\circ C}$, and the dried lipid film was hydrated at the same temperature by vortexing with $\pu{3 mL}$ sterile $\pu{5 mM}$ sodium phosphate buffered saline (PBS), $\mathrm{pH\: 7.4}$. After $\pu{1 h}$ at $\pu{21 ^\circ C}$ the liposome suspension was centrifuged at $\pu{50000 G}$ for $\pu{10 min}$, and the lipid pellet was resuspended in PBS ($\pu{2 mL}$). This procedure was repeated twice, and the cortisol concentration in the final suspension ($\pu{\approx 0 45 mg/mL}$) was determined by the fluorometric method of Zenker and Bernstein.

Further review for water insoluble drug delivery strategies: Read Refs.3-5.

References:

  1. Chee Wai Wong, Bertrand Czarny, Josbert M. Metselaar, Candice Ho, Si Rui Ng, Amutha Veluchamy Barathi, Gert Storm, Tina T. Wong, "Evaluation of subconjunctival liposomal steroids for the treatment of experimental uveitis," Scientific Reports 2018, 8(6604), 11 pages (https://doi.org/10.1038/s41598-018-24545-2).
  2. Nigel C. Phillips, D. Peter Page Thomas, C. Graham Knight, John T. Dingle, "Liposome-incorporated corticosteroids. II. Therapeutic activity in experimental arthritis," Annals of the Rheumatic Diseases 1979, 38(6), 553-557 (http://dx.doi.org/10.1136/ard.38.6.553).
  3. Huabing Chen, Chalermchai Khemtong, Xiangliang Yang, Xueling Chang, Jinming Gao, "Nanonization strategies for poorly water-soluble drugs," Drug Discovery Today 2011, 16(7-8), 354-360 (https://doi.org/10.1016/j.drudis.2010.02.009).
  4. Sandeep Kalepu, Vijaykumar Nekkanti, "Insoluble drug delivery strategies: review of recent advances and business prospects," Acta Pharmaceutica Sinica B 2015, 5(5), 442–453 (https://doi.org/10.1016/j.apsb.2015.07.003).
  5. Jolanda M. van den Hoven, Sophie R. Van Tomme, Josbert M. Metselaar, Bastiaan Nuijen, Jos H. Beijnen, Gert Storm, "Liposomal Drug Formulations in the Treatment of Rheumatoid Arthritis," Molecular Pharmaceutics 2011, 8(4), 1002–1015 (https://doi.org/10.1021/mp2000742).
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