Sciences of Pharmacy

Wahyu Bachtiar, Tyssa Mariyana, Nurul Hidayatri, Bheta Sari Dewi, Ayu Werawati

Topical steroid withdrawal (TSW) is an iatrogenic dermatosis following prolonged topical corticosteroid use, with limited non-steroidal alternatives. This study developed a multi-extract emulgel containing Andrographis paniculata, Tinospora cordifolia, Curcuma longa, and Piper nigrum and screened its nitric oxide (NO)-scavenging activity. Standardized ethanolic extracts were incorporated into eight emulgels (F1–F8) using a 2³ full factorial design, varying A. paniculata (3–5%), T. cordifolia (4–6%), and C. longa (4–6%) with P. nigrum fixed at 10%. Physical characterization showed homogeneous oil-in-water emulgels with pH 5.26–5.90, spreadability 6.7–6.8 cm, and viscosity 12,560–17,120 cP. IC₅₀ values for all formulations exceeded the highest tested concentration (100 µg/mL) without reaching the concentration-response curve plateau, and are reported as > 100 µg/mL compared to 18.48 µg/mL for ascorbic acid. Descriptive ranking placed F4 first, followed by F7 and F8. Exploratory factorial analysis indicated that C. longa levels and the A. paniculata × T. cordifolia interaction drove IC₅₀ variation, showing that higher extract loading did not enhance activity. Because this cell-free assay reflects only direct chemical NO scavenging, findings are strictly preliminary and descriptive. Future validation requires independent runs across an expanded concentration range capturing the full upper plateau. F4 is tentatively proposed as the lead formulation for confirmatory testing and subsequent stability, cell-based, and in vivo studies.

Sciences of Pharmacy

Ade Abiyyatun Mahdiyyah, Mazaya Fadhila, Moh. Firman Irwanto, Ayu Rana Esadini, Wafa Wafa, Alfa Frista Arta, Ira Novita Sari

Solid lipid nanoparticles (SLNs) have been investigated as lipid-based delivery systems to improve the solubility, stability, bioavailability, and delivery of plant-derived phytochemicals to tumors for cancer therapy. However, the available evidence remains heterogeneous and predominantly preclinical. This systematic review aimed to evaluate the formulation strategies, physicochemical characteristics, and therapeutic applications of phytochemical-loaded SLNs in cancer therapy. The review followed the PRISMA 2020 guidelines. Original research articles in English investigating phytochemical-loaded SLNs for cancer therapy were included. Data on formulation composition, preparation methods, physicochemical properties, drug release, in vitro anticancer activity, pharmacokinetics, biodistribution, and in vivo antitumor efficacy were extracted. Risk of bias was assessed using the SYRCLE tool for animal studies and an adapted checklist for in vitro studies. Thirty one articles were included in the qualitative synthesis. Most SLNs had particle sizes in the nanoscale range, approximately 50-350 nm, with encapsulation efficiencies of 43-99% and sustained-release profiles. Encapsulation generally improved cellular uptake and in vitro cytotoxicity in several cancer models. However, evidence of improved bioavailability, active tumor targeting, and in vivo antitumor efficacy remained limited and heterogeneous. Surface modification enhanced cellular uptake or organ accumulation in some studies, but validated tumor-specific targeting was not consistently demonstrated. Overall, phytochemical-loaded SLNs demonstrate potential as delivery platforms; however, clinical translation requires standardized formulations, robust in vivo studies, comprehensive safety evaluations, and clinical trials.

Sciences of Pharmacy

Purwaniati Purwaniati, Rahmana Emran Kartasasmita, Maria Immaculata Iwo, Muhamad Insanu

Natural preservatives derived from medicinal plants require a thorough safety evaluation before they can be used in food. Ginggiang has traditionally been used by the Kuta indigenous community in Ciamis, West Java, Indonesia, to preserve palm sap; however, its safety profile has not been evaluated. In this study, a solid preservative preparation was developed from the decolorized ethanolic extract of ginggiang leaves (SPP-ED), and its safety profile was assessed after repeated oral administration. The study focused on subchronic oral toxicity and identified the target organs affected by repeated exposure to SPP-ED. In a 90-day experiment, both male and female Wistar rats received SPP-ED at doses of 45, 150, or 1500 mg/kg body weight per day. Satellite groups were included to evaluate recovery. Various parameters, including behavioral, hematological, biochemical, urinalysis, organ index, and histopathological evaluations, were systematically analyzed. No mortality was observed during the study. The results showed that subchronic exposure to SPP-ED had sex-specific effects: female rats experienced renal alterations, characterized by changes in urinalysis, elevated blood urea nitrogen and creatinine levels, and signs of tubular degeneration. In contrast, male rats exhibited pulmonary changes, including an increased lung-to-body weight ratio, alveolitis, and fibrosis. The D1 dose (45 mg/kg body weight/day) was the lowest dose at which potentially adverse histopathological changes were observed; however, a definitive NOAEL and LOAEL could not be established. Further studies using lower dose levels are warranted to better characterize the dose-response relationship and establish the NOAEL and LOAEL of SPP-ED.

Sciences of Pharmacy

Yeni Farida, Rizki Amalia Taufany

Potentially inappropriate medications (PIMs) are a common issue in older adults. Older adults often require multiple medications to manage cardiometabolic disease. This study aimed to identify potentially inappropriate medications and potential inappropriate omissions using STOPP/START criteria in older adult patients with cardiometabolic disease. We conducted an observational analytical study using retrospective data at a secondary care teaching hospital in Sukoharjo, Central Java. We included older adult patients admitted to the inpatient wards between January and June 2022. The prescriptions were analyzed using the STOPP/START Criteria 2016. The Chi-square test analysis was performed to examine the association between the number of drugs and the occurrence of PIMs. We included 97 geriatric inpatients. All patients received at least 5 drugs during each admission, 35.06% were classified as having hyperpolypharmacy. Among the 97 patients, 36.08% had PIM prescriptions, and 29.89% had PPOs. There was a statistically significant association between the number of drugs and PIMs in older adults. Compared with patients receiving > 10 medications, those receiving 5–10 medications had lower odds of PIM use (OR 0.409, 95% CI 0.173–0.969; p = 0.040). These findings highlight high medication burden as an important marker for targeted medication review in geriatric inpatients, particularly those with cardiometabolic multimorbidity.

Sciences of Pharmacy

Moh. Firman Irwanto, Arif Budi Setianto, Ade Abiyyatun Mahdiyyah, Maratun Shoaliha, Amzal Mortin Andas, Ashar Prima, Indah Puspitasari, Andi Tenri Nurwahidah, Fauziah H Wada

Tadalafil is a BCS Class II drug with very low aqueous solubility, limiting its oral bioavailability. Solid dispersion technology using polyethylene glycol (PEG) is an effective strategy to enhance solubility. This study aimed to compare the effectiveness of PEG 4000 and PEG 6000 as carriers in amorphous solid dispersions of tadalafil prepared by the melting method. Solid dispersions were prepared at weight ratios (tadalafil:polymer) of 1:1, 1:2, 1:3, and 1:4 for both PEG 4000 and PEG 6000 using the fusion technique (70 °C). The formulations were characterized by Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared (FTIR) spectroscopy. Solubility studies were conducted in distilled water and phosphate buffer (pH 6.8) and analyzed via a validated HPLC method. Solid dispersions with PEG 6000 at a 1:3 ratio (F7) exhibited the highest solubility enhancement, reaching 16.08 ± 0.6 µg/mL in water. For PEG 4000, the 1:2 ratio (F2) was optimal (8.20 ± 1.3 µg/mL). PXRD and DSC analyses confirmed the transformation of crystalline tadalafil into an amorphous state within the polymer matrix. FTIR spectra indicated shifts in N-H and C=O bands, suggesting hydrogen bond formation. In conclusion, PEG 6000 produced a superior solid dispersion for tadalafil compared to PEG 4000. The primary mechanism is the formation of an amorphous system stabilized by hydrogen bonding. This study provides a formulation basis for improving the oral delivery of tadalafil.

Sciences of Pharmacy