Background: This study evaluates transdermal delivery of tamoxifen (TXN) as an alternative to the oral route of administration in treating breast cancer, which is the leading cause of cancer-related death in women globally. Oral TXN, a Class II drug, is associated with first-pass metabolism and serious side effects, including secondary cancers. Objectives: To enhance transdermal delivery, lipid-based transethosomes (TRS) were formulated using three different 2⁴ factorial designs with various non-ionic surfactants, including Tween 20^®, Span 20^®, and Span 80^®. Methods: Optimized TRS formulations were incorporated into HPMC-based gels and characterized for morphology, drug content, pH, viscosity, spreadability, ex vivo skin penetration, and deposition. Additionally, cytotoxicity and stability were assessed. Results: All TXN-TRS gels were suitable for transdermal use; however, Span 20^®-based TRS gel demonstrated the highest skin penetration (40.3 ± 1.5 µg/cm²), representing a 127-fold enhancement rate compared with the non-ethosomal TXN gel. In line with the enhanced penetration profile, cellular studies on MCF-7 cells showed concentration-dependent cytotoxicity, reaching 91.24 ± 1.01% inhibition at 2% w/w after 72 h, with an IC₅₀ value of 0.85 ± 0.02% w/w. Stability testing showed all formulations were more stable under refrigeration than at dry room temperature storage, supporting their potential as preclinical transdermal tamoxifen delivery platforms. Conclusions: Span 20^®-based TXN transethosomal gel markedly enhanced skin penetration while maintaining potent cytotoxic activity, supporting its further preclinical evaluation as a promising transdermal alternative to oral tamoxifen.

Background/Objectives: The formulation development of Isotretinoin (ISN) is limited by its solubility and stability issues. This study aimed to characterise the BCS class II drug ISN, particularly the possible different solid state and formulate amorphous solid dispersion aiming for a supersaturation state. Methods: ISN’s physical states are investigated in its raw form, quench-cooled form, physical mixture with the polymer and corresponding solid dispersion form. Quench-cooled ISN was prepared in situ using DSC. Carrier stabilisation of ISN was attempted using the solid dispersion technique. Hereby, the solid dispersion of drug-polymer PVPVA at a ratio of 1:3 was prepared using the solvent evaporation method. Solid dispersion, physical mixture and raw ISN were characterised for the saturated solubility. Physical characterisation of the samples was performed using DSC, ATR-FTIR and a light microscope. Results: Two polymorphs of ISN (forms I and II) were found in the raw ISN, with form II being thermodynamically more stable. ISN possesses strong crystallinity and resistance to amorphisation under the applied quench-cooling condition without the presence of a carrier system. The conjugated polyene structure in ISN contributes to the polymorphic transformation and isomerisation. The incorporation of PVPVA in the solid dispersion system successfully improved the water solubility (sixfold) of ISN despite a combination of crystalline and amorphous components being present in the system. Conclusions: ISN is a class II drug crystal molecule. Taking advantage of solubility and possibility in the polymorphic transformation of ISN in a binary system, we concluded that ISN could potentially be formulated into its corresponding crystalline solid dispersion form.

Background/Objectives: optimization of the therapeutic efficacy of antidiabetic agents is still a great challenge in the management of type 2 diabetes mellitus (T2DM), and attention is becoming more and more focused on the use of adjunctive agents that help target the drug action beyond the classic glycemic target. This study examined the effect of co-administration of an Artemisia herba-alba Asso (Asteraceae) aqueous extract on the glucose-lowering effect of dapagliflozin, a sodium–glucose cotransporter-2 (SGLT2) inhibitor. Methods: qualitative phytochemical screening and total phenolic and total flavonoid content were used to characterize the aqueous preparation. Male Wistar albino rats were divided into eight groups (10 rats each): four healthy and four diabetic rats induced with streptozotocin (STZ). Vehicle control, oral administration of an aqueous A. herba-alba preparation (0.39 g/kg twice daily), dapagliflozin (0.143 mg/kg/day), or a combination of both was given for 30 days. At baseline and days 7, 14, 21, and 30, glycated hemoglobin (HbA1c) was measured by nephelometry. Parallel fasting blood glucose (FBG) was monitored. Results: the diabetic animals treated with the combination regimen showed the greatest and most sustained decrease in HbA1c (from 4.42 ± 0.40% at baseline to 3.44 ± 0.17% at day 30; p < 0.001) and the greatest decrease in FBG (from 186.0 to 122.2 mg/dL). A. herba-alba monotherapy had little effect on HbA1c and had minimal effect on FBG (214.9 to 217.6 mg/dL); dapagliflozin monotherapy had a modest effect on HbA1c. The untreated diabetic controls (n = 10) showed a progressive increase in HbA1c from 4.45 ± 0.60% at 72 h post-induction to 11.90 ± 0.99% by day 30 (p < 0.001), consistent with delayed hemoglobin glycation relative to the rise in blood glucose. The repeated-measures ANOVA showed a highly significant interaction between time and treatment (p < 0.001). Conclusions: this study showed that the phytochemically defined aqueous A. herba-alba preparation is a beneficial adjunct to SGLT2 inhibitor therapy, an effect not observed with either treatment alone.