This work aimed to develop a three-dimensional printed (3DP) tablet containing glimepiride (GLMP) and/or rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes. Curcumin oil was extracted from the dried rhizomes of Curcuma longa and utilized to develop a self-nanoemulsifying drug delivery system (SNEDDS). Screening mixture experimental design was conducted to develop SNEDDS formulation with a minimum droplet size. Five different semi-solid pastes were prepared and rheologically characterized. The prepared pastes were used to develop 3DP tablets using extrusion printing. The quality attributes of the 3DP tablets were evaluated. A non-compartmental extravascular pharmacokinetic model was implemented to investigate the in vivo behavior of the prepared tablets and the studied marketed products. The optimized SNEDDS, of a 94.43 ± 3.55 nm droplet size, was found to contain 15%, 75%, and 10% of oil, polyethylene glycol 400, and tween 80, respectively. The prepared pastes revealed a shear-thinning of pseudoplastic flow behavior. Flat-faced round tablets of 15 mm diameter and 5.6–11.2 mm thickness were successfully printed and illustrated good criteria for friability, weight variation, and content uniformity. Drug release was superior from SNEDDS-based tablets when compared to non-SNEDDS tablets. Scanning electron microscopy study of the 3DP tablets revealed a semi-porous surface that exhibited some curvature with the appearance of tortuosity and a gel porous-like structure of the inner section. GLMP and RSV demonstrated relative bioavailability of 159.50% and 245.16%, respectively. Accordingly, the developed 3DP tablets could be considered as a promising combined oral drug therapy used in treatment of metabolic disorders. However, clinical studies are needed to investigate their efficacy and safety.

Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr’s index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100–150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions.

Background: Aromatic aldehydes, with their ability to increase the oxygen affinity of sickle hemoglobin, have become important therapeutic agents for sickle cell disease (SCD). One such compound, voxelotor, was recently approved for SCD treatment. Methyl 6-((2-formyl-3-hydroxyphenoxy)methyl) picolinate (PP10) is another promising aromatic aldehyde, recently reported by our group. Like voxelotor, PP10 exhibits O₂-dependent antisickling activity, but, unlike voxelotor, PP10 shows unique O₂-independent antisickling effect. PP10, however, has limited solubility. This study therefore aimed to develop oral and parenteral formulations to improve PP10 solubility and bioavailability. Methods: Oral drug tablets with 2-hydroxypropyl beta cyclodextrin (HP-β-CD), polyvinylpyrrolidone, or Eudragit L100-55 PP10-binary system, and an intravenous (IV) formulation with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) or HP-β-CD, were developed. The pharmacokinetic behavior of the formulations was studied in Sprague-Dawley rats. PP10, a methylester, and its acid metabolite were also studied in vitro with sickle whole blood to determine their effect on Hb modification, Hb oxygen affinity, and sickle red blood cell inhibition. Results: Aqueous solubility of PP10 was enhanced ~5 times with the HP-β-CD binary system, while the TPGS aqueous micelle formulation was superior, with a drug concentration of 0.502 ± 0.01 mg/mL and a particle size of 26 ± 3 nm. The oral tablets showed relative and absolute bioavailabilities of 173.4% and 106.34%, respectively. The acid form of PP10 appeared to dominate in vivo, although both PP10 forms demonstrated pharmacologic effect. Conclusion: Oral and IV formulations of PP10 were successfully developed using HP-β-CD binary system and TPGS aqueous micelles, respectively, resulting in significantly improved solubility and bioavailability.