Knowledge, Perceptions and Attitudes among Sharia Practitioners in Palestine Regarding Halal Pharmaceuticals: An Exploratory Study.

The purpose of this questionnaire-based cross-sectional study was to investigate the knowledge, perceptions, and attitudes regarding halal pharmaceuticals among sharia practitioners in Palestine. A total of 420 sharia practitioners with different educational levels were included. This was a cross-sectional study conducted between March and July 2021 with the use of a standardized, self-administered questionnaire. Volunteers were selected throughout Palestine using a systematic random selection approach. The data were summarized using descriptive statistics (mean, standard deviation, frequency, percentage, median, and interquartile range). The Chi-square and Fisher's exact tests were used to examine the relationship between demographic factors and the knowledge, attitude, and perception scores, respectively. The results revealed that sharia practitioners have relatively good and positive knowledge toward halal pharmaceuticals. The main knowledge of most halal pharmaceuticals was about 50.2%, yet there is still significant latitude in their knowledge of a few issues. The main attitude and perception score was about 96.4%. The results showed a positive and fair correlation between knowledge and attitude (r = 0.153, P < 0.001) and also between knowledge and perception (r = 0.341, P < 0.001). In addition, there is a good correlation between attitude and perception (r = 0.681, P < 0.001). The study concluded that better knowledge of halal pharmaceuticals is associated with positive perceptions and behaviors. The government, pharmaceutical manufacturers, religious scholars, and health care professionals should collaborate to achieve the goal of using halal medications.

Stability of extemporaneously prepared sitagliptin phosphate solution.

Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that is used orally in conjunction with diet and exercise to control sugar levels in type 2 Diabetes Mellitus patients. This study aimed to extemporaneously prepare SiP solution (1% w/v) using pure Sitagliptin phosphate (SiP) powder and assess its stability according to pharmaceutical regulatory guidelines. Four SiP solutions, coded T1, T2, T3, and T4, were extemporaneously prepared using pure SiP powder as a source of API. The most suitable one, in terms of general organoleptic properties, was selected for further investigations, including stability studies. For this last purpose, samples of the T4 solution were kept under two storage conditions, room temperature (25˚C and 60% Relative Humidity) and accelerated stability conditions (40˚C and 75% Relative Humidity). Assay, pH, organoleptic properties, related substances, and microbial contamination were evaluated for 4 consecutive weeks. A High-Performance Liquid Chromatography (HPLC) analytical method was developed and validated to be used for the analysis and quantification of SiP in selected solution formulation. The adopted formula had a pH on the average of 3 to 4. During the stability tests, all pH values remained constant. Furthermore, after 4 weeks of storage under both conditions, the SiP concentration was close to 100%. A stable SiP extemporaneous solution was successfully prepared using pure SiP powder. Patients with swallowing problems who use feeding tubes and are unable to take oral solid dosage forms may benefit from this research. Community pharmacists can prepare the solution using sitagliptin powder as the source of the active ingredient.

Features, applications, and sustainability of lipid nanoparticles in cosmeceuticals.

Cosmeceuticals are a branch of cosmetic products that forms a bridge between cosmetic and drug products. It is a fast-growing branch of the cosmetic industry, especially after the introduction of novel formulation and manufacturing techniques such as lipid nanoparticles (LNPs). These LNPs-based cosmeceutical products offer several advantages such as enhanced bioavailability of cosmeceutical active ingredients (CAIs), improved aesthetic appeal, and stability of the final products. However, the use of these LNPs may raise some concerns about possible side effects of these LNPs and potential hazards to the customer's health. Accordingly, an update that focuses on the use of this important branch of nanoparticles is necessary since most review papers are dealing with all types of nanocarriers in the same review with little focus on LNPs. Therefore, in the current review, a detailed analysis of the advantages and disadvantages of LNPs in this field was highlighted, to emphasize the LNPs-based cosmeceuticals on the market, as well as the potential risk posed by LNPs on exposure and recently introduced regulatory guidelines to address them. In addition, if these products can be a candidate as products that meet the sustainable development goals raised by the UN are discussed.

Synthesis of Rutin Derivatives to Enhance Lipid Solubility and Development of Topical Formulation with a Validated Analytical Method.

BACKGROUND: Rutin is available on the market as a topical formulation for the treatment of several conditions, such as internal bleeding, hemorrhoids, and varicose veins. However, these gels have low solubility and limited bioavailability due to their decreased lipid solubility. OBJECTIVE: In this study, we aimed to synthesize potentially novel lipophilic rutin prodrugs. The suggested library of these rutin prodrugs includes changing the solubility profile to facilitate rutin transport across biological barriers, thereby improving drug delivery through topical application. METHODS: Six rutin derivatives were synthesized based on the ester prodrug strategy. The synthesized compounds were formulated as topical ointments, and their permeability via Franz diffusion was measured. An ultraviolet (UV) analytical method was developed in our laboratories to quantify rutin derivatives both as raw materials and in final dosage forms. The analytical method was then validated. RESULTS: The results of Franz diffusion analyses showed that transdermal permeability increased by 10-fold for decaacetylated rutin compared to the other esterified rutins. A simple analytical method for the analysis of the formulated rutin ester was developed and validated. Moreover, the formulated ointment of decaacetylated rutin in our research laboratory was found to be stable under stability accelerated conditions. Synthesis of potentially more lipophilic compounds would yield novel rutin prodrugs suitable for topical formulation. CONCLUSION: This project provides a synthetic approach for many similar natural products. The research idea and strategy followed in this research project could be adapted by pharmaceutical and herbal establishments.

Formulation, Physical Stability, and the Clinical Effectiveness of Extemporaneous Ivermectin Oral Solution.

Ivermectin is a gamma amino butyric acid (GABA)-gated-Cl-channels modulator, which has been used orally in the treatment of numerous parasitic infections. The study target was to set up a stable, efficient 0.2% w/v ivermectin solution, which would be achieved from pure ivermectin powder as a source of the active pharmaceutical ingredient. Several trial solutions were prepared. The most fitting solution, with respect to its organoleptic properties, was chosen for additional investigation, including the solution's physical stability. Two storage conditions, room temperature (25°C, 60% relative humidity) and accelerated stability chambers (40°C, 75% relative humidity) were subjected to guarantee the physical stability of the solution through the 3-month study period. Furthermore, other quality tests were assessed, (e.g., pH, assay, organoleptic properties, microbial contamination) for the same latter period. Quantification of ivermectin was validated utilizing a high-performance liquid chromatography analytical method. The adopted solution showed accepted organoleptic properties. The pH of the solutions was approximately 5 and remained unchanged during the stability study. The mean percent of remained ivermectin solution was close to 97% ± 0.2 at room temperature. Ivermectin solution was additionally tested for microbial contamination, and it was free from any microbial contamination (E. coli bacteria: Negative/mL, yeast and molds count: <10 cfu/mL and aerobic microbial count results in <10 cfu/mL). The adopted formula showed the best physical stability within at least the three months of storage at both room and accelerated conditions. Ivermectin solution was successfully prepared from its pure powder. This formula provides a stable, efficient oral solution for those who suffer from swallowing difficulties or patients in the intensive care unit who cannot receive the medication in a solid dosage form. Using the suggested formula, community and hospital pharmacists could prepare an effective, high quality ivermectin oral solution using pure ivermectin powder.

Extemporaneous Compounding and Physiological Modeling of Amlodipine/Valsartan Suspension.

METHOD: Amlodipine/valsartan extemporaneous suspension was prepared from available commercial tablets such as Valzadepine®. The dissolution profiles for the extemporaneous preparation and the commercial tablet were determined in different pH media. The physical, chemical, and microbial stability of the compounded formulation was evaluated over one-month period at room temperature. Moreover, in silico modeling using GastroPlus™ software was used to build absorption models for both drugs based on the in vitro dissolution data. The simulated plasma profiles for both active ingredients were compared with the in vivo plasma profiles to examine the similarity of the extemporaneous suspension and the commercial tablets. RESULTS: The amlodipine/valsartan extemporaneous suspension was successfully prepared with acceptable organoleptic properties. The suspension was stable for four-week period preserving its physical and chemical features. The release profiles of valsartan and amlodipine from the suspension were similar to those from source tablet Valzadepine®. In silico modeling predicted the similarity of the extemporaneous suspension and the commercial tablets. CONCLUSION: Amlodipine/valsartan extemporaneous suspension could be prepared from available commercial tablets. Moreover, GastroPlus™ can be applied along with the in vitro dissolution in order to affirm similarity in extemporaneous compounding situations.

A Comprehensive Review on Pharmaceutical Film Coating: Past, Present, and Future.

Pharmaceutical film coating is considered a key part in the production of solid pharmaceutical dosage forms since it gives superior organoleptic properties products. In addition, it can improve the physical and chemical stability of dosage forms, and modify the release characteristics of the drug. Several troubleshooting problems such as twinning mottling, chipping, etc., may arise during or after or even during the shelf life of the film coated dosage forms. These troubleshooting problems may be due to tablet core faults, coating formulation faults and/or coating process faults. These problems must be overcome to avoid unnecessary product problems. Film coating as well as other parts of the pharmaceutical technology is subjecting to continuous innovation. The innovation may be at different levels including pharmaceutical excipients, processes, software, guidelines and equipment. In fact, of particular note is the growing interest in process analytical technology, quality by design, continuous coating processing and the inclusion of new ready for use coating formulations. In this review, we tried to explore and discuss the status of pharmaceutical film coating, the challenges that face this manufacturing process and the latest technological advances in this important manufacturing process.

Identification of substandard drug products using electronic tongue: cefdinir suspension as a pilot example.

BACKGROUND: Electronic tongue (ET) is a well-established technology that is used to detect the taste of a food or a medicinal product and to differentiate between different products based on their tastes. In addition, it can be used to monitor environmental parameters and biochemical and biological processes. PURPOSE: This study aims to assess any correlation between the results of pharmacopeial quality control (ie, assay, impurities, and dissolution, etc) and ET analysis for reconstituted cefdinir (CR) suspension over 10 days (ie, shelf-life). METHODS: The reconstituted CR suspension was tested for several quality attributes such as dissolution behavior, pH, assay, related substances, and microbial contamination. An HPLC analytical method was verified and then used for chemical analysis. The taste of CR reconstituted suspension was followed over 10 days and was then compared with the quality control results. Moreover, Pearson's correlation test was used to find a correlation between chemical analysis results and ET results. RESULTS: Pearson's test of correlation showed a significant correlation (p-value <0.05) between the conventional chemical analysis results (% of CR, % of preservative, % of released CR, % of total impurities and % of total undefined impurities in the reconstituted suspension) with the change of their taste (ie, % pattern discrimination index). ET was able to correlate the results of stability of CR suspension with the change in the taste of the suspension during the shelf life of the reconstituted suspension. CONCLUSION: The obtained results may suggest the use of ET as a new tool for a rapid assessment of the general quality of a suspension. Moreover, such results would suggest the use of ET to identify fake or substandard products, especially those have been stored under inappropriate storage conditions.

Evaluating the potential use of electronic tongue in early identification and diagnosis of bacterial infections.

BACKGROUND: Electronic tongue (ET) is a simple device that may have some applications in the medical field as an alternative tool to traditional diagnostic methods. The aim of this study is to evaluate the potential use and accuracy of ET in the diagnosis of certain bacterial infections. METHODS: An alpha-Astree ET was used for the detection of known bacterial strains Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and Pseudomonas aeruginosa (ATCC 27853) which were tested at three-time intervals; 15, 18, and 24 hrs (hr). This was used to build a qualitative and quantitative mathematical model to detect the presence of bacteria at the earliest possible time. When the model is robust, new unknown samples were tested after 15 hrs of bacterial growth. Samples were identified using multivariate data analysis techniques. RESULTS: Principal Component Analysis (PCA) scores showed that ET can distinguish between the three bacteria at different times 15, 18, and 24 hrs using different sensors. In the PCA scores plots, the discrimination index was 83% at 15 hrs, 88% at 18 hrs, and 96% at 24 hrs, the variances explained by the two principal components were 84%, 99%, and 97% at 15, 18, and 24 hrs, respectively. Fifteen hours was the earliest time at which the bacteria could be detected. Then six samples of E.coli (as unknown samples) were tested after 15 hrs of inoculation, the two discrimination function explained about 100% of the variance (ie, 79.7+22.3%) and all unknown samples were identified as E.coli. CONCLUSION: ET could differentiate between types of bacteria in addition to identifying unknown bacterial cultures (E. coli) at times shorter than that required in the current culture-based methods (24-48 hrs), this could be of a great value in early diagnosis of life-threatening infections.

Herbal remedies used for the treatment of infertility in males and females by traditional healers in the rural areas of the West Bank/Palestine.

BACKGROUND: Infertility is considered one of the global public health problems and during human history, it is also considered one of the unsolved problems of the continuous human race. This study aimed to collect and document the ethnopharmacological data on herbal remedies, which traditionally used by Palestinian healers in the rural areas of the West Bank area for the treatment of infertility in males and females. METHODS: Using a semi-structured questionnaire, an ethnopharmacological survey of medicinal plants used for the treatment of infertility in the West Bank area of Palestine was investigated. This survey involved 51 traditional healers which were interviewed in rural areas from 9 Palestinian regions. RESULTS: Information about 31 plants used in the treatment of infertility in females and 24 plants used in the treatment of infertility in males were collected. This information including names of plants, parts used, mode and methods of preparation which were obtained from 51 traditional healers interviewed in rural areas of 9 regions of the West Bank/Palestine. This investigation is the first scientific work in the Middle East area which collected information about herbal remedies used by local Palestinian traditional healers for the treatments of infertility in males and females. The highest Frequency of Citation (FC) of herbal remedies used in case of infertility in females, were 98.04% for pollen grains from Ceratonia siliqua, 88.24% for Anastatica hierochuntica fruits and 84.31% for Parietaria judaica leaves, while the highest Frequency of Citation (FC) of herbal remedies used in case of infertility in males were 96.08% for Ferula hermonis roots, 88.24% for Phlomis brachyodon leaves and 86.27% for Phoenix dactylifera pollen grains. CONCLUSION: Herbal healers in the West Bank area of Palestine have a wide range of herbal remedies used in case of infertility in males and in females. Unfortunately, most of them lack scientific evidence of pharmacological or toxicological nature. Therefore, the information obtained in this study can serve as a scientific base for further investigations to determine their efficacy and safety which might contribute to better integration of Palestinian traditional medicine into the global health system in the future.

Depigmentation and Anti-aging Treatment by Natural Molecules.

Natural molecules are becoming more accepted choices as cosmetic agents, many products in the market today claim to include natural components. Plants include many substances that could be of a value in the whitening of the skin and working as anti-aging agents. A wide range of articles related to natural skin whitening and anti-aging agents have been reviewed. Many plant-derived and natural molecules have shown to affect melanin synthesis by different mechanisms, examples include Arbutin, Ramulus mori extract, Licorice extract, Glabridin, Liquiritin, Kojic acid, Methyl gentisate, Aloesin, Azelaic acid, Vitamin C, Thioctic acid, Soya bean extracts, Niacinamide, α and ß-hydroxy acids, Lactic acid, Chamomile extract, and Ellagic acid. Some of the widely used natural anti-aging products as natural antioxidants, collagen, hyaluronic acid, and coenzyme Q can counteract the effects of reactive oxygen species in skin cells and have anti-aging properties on the skin. It was concluded that many natural products including antioxidants can prevent UV-induced skin damage and have whitening and anti-aging effects. It is very important to develop and stabilize appropriate methods for the evaluation of the whitening and anti-aging capacity of natural products and their exact mechanism of action to ensure real efficacy based on evidence-based studies. The attention should be oriented on the formulations and the development of an appropriate vehicle to ensure suitable absorption of these natural products in addition to evaluating the suitable concentration of these molecules required having the desired effects without causing harmful side effects.

The Neuroprotective Role of Origanum syriacum L. and Lavandula dentata L. Essential Oils through Their Effects on AMPA Receptors.

Lavandula dentata L. and Origanum syriacum L. essential oils have numerous health benefits and properties, such as possessing common components with a variant degree of depressive actions in the central nervous system. We investigated the depressive property of these oils on AMPA receptors, which are responsible for most of the fast-excitatory neurotransmission in the CNS and play a critical role in synaptic plasticity. Since excessive activation of AMPARs has been linked to neurotoxicity leading to various pathologies, we hypothesize that these oils have a neuroprotective role by acting directly on the kinetics of AMPARs. Using Gas Chromatography-Mass Spectrometry (GC/MS) and patch-clamp electrophysiology, the essential oils of L. dentata flowers and O. syriacum leaves were characterized and the whole cell currents were measured with and without the administration of the oils onto HEK293 cells. The current study results showed that the biophysical properties of AMPA receptor subunits showed a decrease in desensitization rate of GluA1 and GluA2 homomers, using O. syriacum, while administering L. dentata oil decreased the desensitization rate of GluA1 and GluA2 homomers, as well as GluA1/2 heteromers. As for the deactivation rate, both oils slowed the deactivation kinetics of all AMPA receptor subunits. Intriguingly, between the two oils, the effect of desensitization and deactivation was of a greater significance for L. dentata oil than O. syriacum. Our data suggest that the two oils contain components that are essential to identify, as those active components underlie the oils' neuronal depressive properties reported, and to extract them to synthesize a potent neuroprotective drug to treat neurological diseases potentially.

Rapid, cost-effective and organic solvent-free production of biologically active essential oil from Mediterranean wild Origanum syriacum.

BACKGROUND: Origanum syriacum (O. syriacum) is a very popular edible and medicinal plant in the East Mediterranean countries. The aims of the current study were to use microwave-ultrasonic assisted hydrodistillation (MUAHD) method to produce essential oils (EOs) from wild O. syriacum samples collected from four different geographical areas in The West Bank using water as a solvent, determine the phytochemical profile using GC-MS analysis and assess their antioxidant and antibacterial potential. METHODS: Essential oils were produced using MUAHD method. Gas chromatography coupled with mass spectrometer detector (GC-MS) was employed for phytochemical analysis. In vitro antibacterial and antioxidant potentials were carried out. RESULTS: Differences in the EOs yield among the four Origanum samples were observed. GC-MS analysis of EOs revealed terpenes as the major constituents; monoterpenes (22-56%) and oxygenated monoterpenes (28-57%). Thymol, α-terpinene and carvacrol represent the bulk of all phytochemicals detected by GC-MS analysis. γ-Terpinene-rich EOs, exhibited the highest antioxidant capacity. Thymol-rich EOs were found to be most effective against Staphylococcus aureus and Methicillin-Resistant Staphylococcus aureus (MRSA) (MIC 390 µg/mL). Alpha-terpinene-rich chemotype EOs exhibited the highest inhibitory effect of Pseudomonas aeruginosa (MIC of 1560 µg/mL). Interestingly, γ-terpinene-rich EO showed promising antibacterial properties against Enterococcus faecium (MIC 97 µg/mL) and a powerful anti-oxidant effect (91.45% ±2.30). CONCLUSION: The current study supports the use of MUAHD as a time-saving, cost-effective, environment-friendly method for production of high quality O. syriacum EO for potential use as a natural complementary treatment and in the prevention of bacterial infections as well as oxidation by free radicals without compromising the quantity.

Evaluation of food effect on the oral absorption of clarithromycin from immediate release tablet using physiological modelling.

BACKGROUND: Food may affect the oral absorption of drugs. PURPOSE: The aim of the present study was to investigate the influence of food on the oral absorption of clarithromycin by evaluating the effect of media parameters, such as pH, bile secretions and food composition, on the release of the drug from immediate release tablets, using in vitro and in silico assessments. METHOD: The solubility, disintegration and dissolution profiles of clarithromycin 500 mg immediate release tablets in compendial media with/without the addition of a homogenized FDA meal as well as in biorelevant simulated intestinal media mimicking fasting and fed conditions were determined. These in vitro data were input to GastroPlus™, which was used for developing a physiological absorption model capable of anticipating the effect of food on clarithromycin absorption. Level A in vitro-in vivo linear correlations were established using a mechanistic absorption modelling based deconvolution approach. RESULTS: The pH of the media has a profound effect on clarithromycin solubility, tablet disintegration and drug release. Clarithromycin has lower solubility in biorelevant media compared with other media, due to complex formation with bile salts. Clarithromycin tablets exhibited prolonged disintegration times and reduced dissolution rates in the presence of the standard FDA meal. The simulation model predicted no significant food effect on the oral bioavailability of clarithromycin. The developed IVIVC model considered SIF, acetate buffer and FaSSIF media to be the most relevant from the physiological standpoint. CONCLUSION: The intake of a standard FDA meal may have no significant effect on the oral bioavailability of clarithromycin immediate release tablet.

Impact of formulation variables on weight uniformity of scored tablets using factorial design.

Maintaining safety and efficacy is an important task when splitting a tablet. This Pharmacy practice affords the patient with unavailable required dose, easy swallowing, and cost-saving measure. To access the role of formulation variables on the weight uniformity test of halves tablets. Uncoated and coated placebo tablets were prepared using wet granulation technique. After compression, hardness, disintegration time, friability and weight variation were evaluated according to the USP test. Both coated and uncoated tablets were dived and the obtained halves were weighed and the uniformity of halves was assessed for each kind of tablets. Despite the hardness, size, tablet shape (oval, disc, capsule), all of them passed the splitting test except for the disc shape which showed %RSD higher than 6%. However, hardness and the coating had a generally positive trend on tablet breaking since they gave low% RSD. These findings suggest that the disc shape particle is not suitable for breaking. In addition, film coating, as well as high hardness may give better uniformity of the obtained halves, since a decrease in the calculated %RSD was observed.

Corrigendum to "GC Method Validation for the Analysis of Menthol in Suppository Pharmaceutical Dosage Form".

[This corrects the article DOI: 10.1155/2017/1728414.].

Formulation and In Vitro, In Vivo Correlation Between Two Candesartan Cilexetil Tablets.

In this study, the in vitro and in vivo interchangeability between generic candesartan 16 mg and the branded formulation was assessed. The in vitro release of these products was conducted in 3 pH media (1.2, 5.0, and 6.8), and similarity factors (f2 ) were calculated. This bioequivalence study was a randomized, 2-period crossover study that included 42 healthy adult male subjects under fasting conditions with a 9-day washout. The pharmacokinetic (PK) parameters AUC0-last , AUC0-∞ , and Cmax , tmax , and the elimination half-life time were assessed based on the plasma concentrations of candesartan, using a newly developed and validated liquid chromatography-tandem mass spectrometry bioanalytical method with acceptable degrees of linearity, sensitivity, precision, and accuracy. The geometric mean (ng·h/mL) of the AUC0-∞ for the test and brand was 1595.49 and 1620.54, respectively, and the Cmax (ng/mL) was 160.91 and 160.88, respectively. The 90%CIs of geometric mean ratios (test-to-reference ratios) were 98.26%, 98.45%, and 99.86% for AUC0-last , AUC0-∞ , and Cmax respectively. These PK parameters lie within the US Food and Drug Administration- and European Medicines Agency-specified bioequivalence limit (80%-125%). Both products were well tolerated by all the subjects. The tested drug product was bioequivalent to the reference drug and had the same safety profile.

Does GastroPlus Support Similarity and Dissimilarity Factors of in vitro-in vivo Prediction in Biowaiver Studies? A Lower Strength Amlodipine As a Model Drug.

BACKGROUND: Many generic pharmaceutical products are currently available on the market place worldwide. Recently, there is a growing concern on the quality and efficacy of generic products. However, health care professionals such as physicians and pharmacists are in difficult situations to choose among alternatives. PURPOSE: The aim of this study is to assess the effectiveness of the in silico technique (Gastro Plus®) in the biowaiver study and whether similarity and dissimilarity factors (f 2 and f 1 respectively) are effective in this regard. METHOD: The concentration of amlodipine in the sample was calculated by comparing the absorbance of the sample with that of a previously prepared amlodipine standard solution using validated HPLC method. The dissolution profile for each product (brand and generics) was constructed. The similarity (f2) and dissimilarity (f 1) factors were calculated for the generic product according to equation 1 and 2. GastroPlus™ software (version 9.0, Simulations Plus Inc., Lancaster, CA, USA) was used to predict the absorption profiles of amlodipine from the generic product Amlovasc® and the reference Norvasc®. CONCLUSION: These results may provide a rationale for the interchangeability between the RLD and generic version based on in vitro release profiles in silico technique especially in a lower strength dose drug.

Covalent functionalization of SWCNT with combretastatin A4 for cancer therapy.

Single walled carbon nanotubes (SWCNT) are currently under intensive investigation by many labs all over the world for being promising candidates for cancer chemotherapy delivery. On the other hand, combretastatin A4 (CA4) is an anticancer drug that induces cell apoptosis by inhibiting tubulin polymerization. However, it has the disadvantage of low water solubility and the non-selective targeting. Therefore, we aim to create nano-drug from the functionalization of SWCNT covalently with CA4 through click reaction in the presence of tetraethylene glycol linker in order to improve its dispersibility. Scanning electron microscopy and transmission electron microscopy showed good dispersibility of the functionalized SWCNT with diameters of 5-15 nm. Moreover, thermogravometric analysis showed that the efficiency of SWCNT functionalization was around 45%. The in vitro release profile of CA4 at physiological conditions showed that approximately 90% of the loaded drug was released over 50 h. After that MTS test was used to determine the suitable concentration range for the in vitro investigation of the SWCNT-CA4. After that the cytotoxic activity of the SWCNT-CA4 was evaluated by flow cytometry using annexin V/propidium iodide (PI) test. In comparison with free CA4, SWCNT-CA4 treatment demonstrated a significant increase in necrotic cells (around 50%) at the expense of the proportion of the apoptotic cells. Moreover, cell cycle PI test demonstrated that free CA4 and SWCNT-CA4 caused G2/M arrest. However with CA4 treatment higher proportion of cells were in the S-phase while with SWCNT-CA4 treatment greater proportion of cells appeared to be in the G1-phase. Taken together, the provided data suggest that the novel SWCNT-CA4 has a significant anticancer activity that might be superior to that of free CA4.

The Taste of Commercially Available Clarithromycin Oral Pharmaceutical Suspensions in the Palestinian Market: Electronic Tongue and In Vivo Evaluation.

Background: The taste of oral liquid dosage forms is a crucial factor that impacts paediatric patient compliance. The electronic tongue (ET) is an emerging tool that could be useful in taste assessment in order to minimize the involvement of humans in such evaluations. Purpose: The aim of this study is to evaluate the taste of commercially available clarithromycin (CM) oral pharmaceutical suspensions in the Palestinian market. Method: Commercially available CM suspensions (the brand Klacid® and two generic K1 and K2) were assayed using the high performance liquid chromatography (HPLC) method. Then, the taste of these products was assessed using alpha-astree ET. In addition, an in vivo taste assessment was conducted on paediatric patients by a hedonic panel test. Moreover, volunteering community pharmacists were asked to rank the taste of these three products according to their experience from the best to the worst. Results: All suspension products had a CM concentration not less than 98% of the label amount. The ET results coupled with the principal component analysis (PCA) showed a very clear discrimination of the samples with different distances between groups (p-values < 0.001). Suspensions were in the following order in terms of taste: Klacid® > K1 > K2. Moreover, The pattern discrimination index between (K1 and Klacid®), (K1 and K2) and (Klacid® and K2) were 8.81%, 65.75%, and71.94%, respectively which suggests that K1 and Klacid® are the most similar preparations in terms of taste. Interestingly, these results were in excellent agreement with the pharmacist ranking and patient acceptance test. Conclusions: The evaluated preparations showed significantly different taste within the order of Klacid® > K1 > K2, as suggested by both the ET and in vivo results. Moreover, our results confirm the capability of alpha-astree ET in the taste assessment of oral suspensions and in predicting volunteer responses, which highlights its beneficial use as an in vitro taste assessment tool and as an alternative to human-based taste evaluations.