Permeability Enhancement of Methotrexate Transdermal Gel using Eucalyptus oil, Peppermint Oil and Olive Oil(Conference Paper )#

Objective: the idea of this study to improve transdermal permeability of Methotrexate using eucalyptus oil, olive oil and peppermint oil as enhancers.Method: eucalyptus oil (2% and 4%), peppermint oil (2% and 4%) and olive oil (2% and 4%) all used as natural enhancers to develop transdermal permeability of Methotrexate via gel formulation. The gel was subjected to many physiochemical properties tests. In-vitro release and permeability studies for the drug were done by Franz cell diffusion across synthetic membrane, kinetic model was studied via korsmeyer- peppas equation.Result: the results demonstrate that safe, nonirritant or cause necrosis to rats' skin and stable till 60 days gel was successfully formulated.Methotrexate penetration alone without enhancer is only about 20%, while using enhancers reach to 85%, 99% and 90% with eucalyptus oil 4%, peppermint oil 4% and olive oil 4% respectively after 24 hours.Conclusion: Methotrexate transdermal gel was prepared and evaluated fruitfully in-vitro with a good permeation across semipermeable membrane. The results indicated that using of peppermint oil as enhancer have superiority to enhance the transdermal permeation of the Methotrexate.

Preparation of Curcumin Hydrogel Beads for the Development of Functional Kulfi, a Tailoring Delivery System

Curcumin has been demonstrated to have biological activities and its fortification in food products is an important strategy to deliver bioactive ingredients at target sites. However, studies have documented a curcumin low bioavailability and low intake. Hence, combining functional ingredients with food should be needed to prevent widespread nutrient intake shortfalls and associated deficiencies. Thus, curcumin was encapsulated in calcium-alginate and their characteristics as well as in vitro release behavior of curcumin hydrogel beads (CHBs) was studied. Moreover, CHBs were fortified in development of functional Kulfi and their quality characteristics were studied. The encapsulation efficiency was up to 95.04%, indicating that most of the curcumin was entrapped. FTIR shifts in the bands were due to the replacement of sodium ions to the calcium ions. In vitro release (%) for CHBs was found to be 67.15% after 2 h, which increased slightly up to 67.88% after 4 h. The average swelling index of CHBs was found to be 10.21 to 37.92 from 2 to 12 h in PBS (pH 7.40). Control and Kulfi fortified with CHBs showed no significant difference (p > 0.05) in colour (L = 73.03 and 75.88) and the melting rate (0.88 mL/min and 0.63 mL/min), respectively. Standard plate count was reduced in the Kulfi fortified with CHBs (13.77 × 104 CFU/mL) with high sensory score for overall acceptability (8.56) compared to the control (154.70 × 104 CFU/mL). These findings suggested the feasibility of developing CHBs to mask the bitterness, enhance the solubility, and increase the bioavailability in gastrointestinal conditions. Additionally, Kulfi could be a suitable dairy delivery system for curcumin bioactive compounds.

QUALITY CONTROL TESTING OF CONVENTIONAL CLOPIDOGREL BISULFATE TABLETS MARKETED IN IRAQ

Objective: This study was employed to evaluate the quality of marketed oral tablets containing clopidogrel bisulfate. Tablets produced by various companies and commercialized in the Iraq market were used in the study. Methods: Batches of clopidogrel bisulfate conventional tablets (containing 75 mg of drug) were exposed to the quality control tests. These tests involved friability, weight variation, hardness, drug content, disintegration time, and in vitro release study; these tests were conducted depending on USP pharmacopeia. Results: The data indicate that all batches of clopidogrel bisulfate complied with the limitations of USP pharmacopeia for variation of weight, results of the hardness of tablets were 7.2-9.6 Kg/cm2. Friability value (% loss) was less than one, which was within the required limits. The time of disintegration was less than 25 min in both artificial gastric fluid (AGF) and artificial intestinal fluid (AIF). Drug content was observed between 97.1 % and 99.8 %, indicating compliance with the limits of pharmacopeia (85-115 %). An in vitro release study of batches was greater than 80 % within 25 min. Conclusion: All batches of clopidogrel bisulfate were manufactured within the criteria of tablet manufacturing. The quality control tests of tablets showed acceptable pharmaceutical properties (effectiveness and safety) that lie within the limits of USP pharmacopeia.

pH-Responsive Liposomes of Dioleoyl Phosphatidylethanolamine and Cholesteryl Hemisuccinate for the Enhanced Anticancer Efficacy of Cisplatin

The current study aimed to develop pH-responsive cisplatin-loaded liposomes (CDDP@PLs) via the thin film hydration method. Formulations with varied ratios of dioleoyl phosphatidylethanolamine (DOPE) to cholesteryl hemisuccinate (CHEMS) were investigated to obtain the optimal particle size, zeta potential, entrapment efficiency, in vitro release profile, and stability. The particle size of the CDDP@PLs was in the range of 153.2 ± 3.08–206.4 ± 2.26 nm, zeta potential was −17.8 ± 1.26 to −24.6 ± 1.72, and PDI displayed an acceptable size distribution. Transmission electron microscopy revealed a spherical shape with ~200 nm size. Fourier transform infrared spectroscopic analysis showed the physicochemical stability of CDDP@PLs, and differential scanning calorimetry analysis showed the loss of the crystalline nature of cisplatin in liposomes. In vitro release study of CDDP@PLs at pH 7.4 depicted the lower release rate of cisplatin (less than 40%), and at a pH of 6.5, an almost 65% release rate was achieved compared to the release rate at pH 5.5 (more than 80%) showing the tumor-specific drug release. The cytotoxicity study showed the improved cytotoxicity of CDDP@PLs compared to cisplatin solution in MDA-MB-231 and SK-OV-3 cell lines, and fluorescence microscopy also showed enhanced cellular internalization. The acute toxicity study showed the safety and biocompatibility of the developed carrier system for the potential delivery of chemotherapeutic agents. These studies suggest that CDDP@PLs could be utilized as an efficient delivery system for the enhancement of therapeutic efficacy and to minimize the side effects of chemotherapy by releasing cisplatin at the tumor site.

Formulation of Nano/Micro-Carriers Loaded with an Enriched Extract of Coffee Silverskin: Physicochemical Properties, In Vitro Release Mechanism and In Silico Molecular Modeling

Designing strategies for an effective transformation of food waste into high-value products is a priority to address environmental sustainability concerns. Coffee silverskin is the major by-product of the coffee roasting industry, being rich in compounds with health benefits. Such composition gives it the potential to be transformed into high-value products. In this study, coffee silverskin extracts were enriched, regarding caffeine and chlorogenic acid contents, by adsorbent column chromatography. The compounds content increased 3.08- and 2.75-fold, respectively, compared to the original extract. The enriched fractions were loaded into nano-phytosomes or cholesterol-incorporated nano-phytosomes (first coating layers) to improve the physiochemical properties and permeation rate. These nano-lipid carriers were also subjected to a secondary coating with different natural polymers to improve protection and stability against degradation. In parallel, and for comparison, different natural polymers were also used as first coating layers. The produced particles were evaluated regarding product yield, encapsulation efficiency, loading capacity, particle size, surface charge, and in vitro release simulating gastrointestinal conditions. All samples exhibited anionic surface charge. FTIR and molecular docking confirmed interactions between the phytoconstituents and lipid bilayers. The best docking score was observed for 5-caffeoylquinic acid (chlorogenic acid) exhibiting a stronger hydrogen binding to the lipid bilayer. Among several kinetic models tested, the particle release mechanism fitted well with the First-order, Korsmeyer–Peppas, and Higuchi models. Moreover, most of the formulated particles followed the diffusion-Fick law and anomalous transport.