Decanol

The model APIs for this study were RTV (Desano Pharmaceuticals, China) and LPV (Arene Life Sciences, India). The polymers for the preparation of the ASDs were either Kollidon® VA 64 fine (PVPVA, BASF, Germany) or the three different grades of AQOAT® LMP, MMP and HMP (HPMCAS, Shin Etsu, Japan). The film-coated tablet Kaletra® 200/50 mg was chosen as reference product. Fasted State Simulated Gastric Fluid (FaSSGF) and Fasted State Simulated Intestinal Fluid (FaSSIF) used as biorelevant dissolution media were prepared using ready-to-use powder mixtures (Biorelevant.com, United Kingdom). For each experiment, the media were freshly prepared according to the supplier manual. Decanol (Sigma Aldrich Chemie GmbH, Germany) was utilized as organic phase in the biphasic dissolution setup. Ammonium acetate, methanol HPLC grade and hydrochloric acid (all VWR Chemicals, Germany) were used for the preparation of the mobile phase for HPLC analysis. Polylactide (PLA) (Bavaria Filaments, Germany) was used as material for the additional 3D printed paddle for the biphasic dissolution studies.

Mn(CH₃COO)₃-2H₂O (99%), Ni(CH₃COO)₂-4H₂O (99%), 1-octadecene (90%), myristic acid (99%), decanol (98%), MnO (99.99%), Mn₃O₄ (97%), Mn₂O₃ (99.9%), NaH₂PO₄-H₂O (99.0%, ACS reagent), and Na₂HPO₄-7H₂O (98.0–102.0%, ACS reagent) were purchased from Sigma Aldrich. Ni(NO₃)₂–6H₂O (99.9985%), MnO₂ (99.9%), and Pt foil (99.997%) were purchased from Alfa Aesar. Acetone (99.5%), toluene (99.5%), hexane (95%), cyclohexane (99.5%), and ethanol (99.5%) were purchased from Daejung Chemicals. All chemicals used as received without further purification. Fluorine doped tin oxide coated glass (FTO) with the surface resistivity of 8 Ω sq^–1 was obtained as 1.0 cm × 1.5 cm pre-cut glass pieces.

APR (purity: 99.6%; MW: 460.5 g/mol) was acquired from Wuhan Senwayer Century Chemical (Wuhan, China). Gattefossé (Barcelona, Spain) supplied Transcutol^® P [Diethylene glycol monoethyl ether]. The permeation promoters Azone^® [1-dodecylazacycloheptan-2-one] was supplied by Durham Pharmaceuticals (Durham, UK). Carene [3-Carene], Decanol [1-Decanol], Limonene [(S)-4-Isopropenyl-1-methyl cyclohexene], Menthone [(2S,5R)-2-Isopropyl-5-methyl cyclohexanone], Nonane [n-Nonane], Pinene [(+)-α-Pinene], and Squalene [2,6,10,15,19,23-Hexamethyltetracosane] were purchased from Sigma Aldrich (Madrid, Spain). Reagents for histological procedures were purchased from Sigma and Thermo Fisher Scientific (Barcelona, Spain). Reagents for cellular assays, HaCaT cell lines, and 3-[4,5-Dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) cell-proliferation assay were obtained from Gibco (Cacavelos, Portugal), Cell Line Services (Eppelheim, Germany), and Sigma (Barcelona, Spain), respectively. Ultrapure water was obtained from Water Millipore MilliQ purification system (Millipore Corporation, Burlington, VT, USA), and all the other chemical reagents used were analytical grade.

HB was purchased from Capot Chemical Company Limited (Hangzhou, China). The permeation enhancers carene ((+)-3-carene), cetiol (decyltetradecyl ethylhexanoate), decanol (decyl alcohol), limonene ((S)-4-isopropenyl-1-methyl cyclohexene), linoleic acid (9-cis,12-cis-linoleic acid), menthone ((2S,5R)-2-isopropyl-5-methylcyclohexanone) and nonane (n-nonane) were acquired from Sigma Aldrich (Madrid, Spain) and Azone^® (1-dodecylazacycloheptan-2-one) from Durham Pharmaceuicals (Durham, UK). Transcutol^® (diethylene glycol monoethyl ether) was kindly given by Gattefossé (Barcelona, Spain). MilliQ Plus system was used to obtain purified water. All the other chemical reagents used were of analytical grade.

PF was supplied by Alcon Cusi (Barcelona, Spain); LAS (PEG-8 Caprylic/Capric Glycerides) and PAT (Precirol^® ATO 5 (glycerol mono, di and tripalmitostearate)) were gifted by Gattefossé (Gennevilliers, France); and Castor oil and Tween^® 80 were purchased from Sigma-Aldrich. The penetration enhancers, linoleic acid (9-cis,12-cis-linoleic acid), decanol (decyl alcohol), menthone ((2S,2R)-2-isopropyl-5-methylcyclohexanone), nonane (n-nonane), pyrrolidone (N-Dodecylpyrrolidone), octanoic acid, squalene (2,6,10,15,19,23-hexametyltetracosane), and cineol were acquired from Sigma Aldrich (Madrid, Spain).
The HaCat was provided by Cell Lines Service (CLS, Eppelheim, Germany) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) used for cell viability was acquired from Invitrogen Alfagene^® (Carcavelos, Portugal). The purified water used in all the experiments was obtained from a MilliQ Plus System (Millipore Corporation, Bedford, MA, USA). All other chemicals and reagents used in the study were of analytical or HPLC-grade (Fischer Chemical, Loughborough, UK).