Dalia A. Hamdy

HPTLC Determination of Three Gliptins in Binary Mixtures with Metformin.

A single, simple, selective and validated high performance thin layer chromatographic (HPTLC) method was developed for the determination of either linagliptin (LGP), saxagliptin (SGP) or vildagliptin (VGP) in their binary mixtures with metformin (MET) in pharmaceutical preparations using environmentally preferable green mobile phase system. Separation was carried out on Merck HPTLC aluminum sheets of silica gel 60 F254 using methanol-0.5% w/v aqueous ammonium sulfate (8 : 2, v/v) as mobile phase. Densitometric measurement of the spots was performed at 225 nm for LGP/MET mixture and at 208 nm for both SGP/MET and VGP/MET mixtures. The linear regression analysis data were used for the regression line in the range of 0.05-0.5 µg/band for LGP and SGP and 0.2-2 and 5-40 µg/band for VGP and MET, respectively. The method was validated and showed good performances in terms of linearity, limits of detection and quantitation, precision, accuracy, selectivity and specificity. The calculated percentage relative error values and percentage relative standard deviation for intra- and interday precision studies did not exceed 2%. The developed method was satisfactorily applied for the analysis of pharmaceutical preparations and proved to be specific and accurate for the quality control of the cited drugs in their dosage forms.

High Performance Liquid Chromatographic Assay for the Simultaneous Determination of Posaconazole and Vincristine in Rat Plasma

Purpose. Developing a validated HPLC-DAD method for simultaneous determination of posaconazole (PSZ) and vincristine (VCR) in rat plasma. Methods. PSZ, VCR, and itraconazole (ITZ) were extracted from 200 μL plasma using diethyl ether in the presence of 0.1 M sodium hydroxide solution. The organic layer was evaporated in vacuo and dried residue was reconstituted and injected through HC-C18 (4.6 × 250 mm, 5 μm) column. In the mobile phase, acetonitrile and 0.015 M potassium dihydrogen orthophosphate (30 : 70 to 80 : 20, linear gradient over 7 minutes) pumped at 1.5 mL/min. VCR and PSZ were measured at 220 and 262 nm, respectively. Two Sprague Dawley rats were orally dosed PSZ followed by iv dosing of VCR and serial blood sampling was performed. Results. VCR, PSZ, and ITZ were successfully separated within 11 min. Calibration curves were linear over the range of 50–5000 ng/mL for both drugs. The CV% and % error of the mean were ≤18% and limit of quantitation was 50 ng/mL for both drugs. Rat plasma concentrations of PSZ and VCR were simultaneously measured up to 72 h and their calculated pharmacokinetics parameters were comparable to the literature. Conclusion. The assay was validated as per ICH guidelines and is appropriate for pharmacokinetics drug-drug interaction studies.

A Comparative Study of Newly Developed HPLC-DAD and UHPLC-UV Assays for the Determination of Posaconazole in Bulk Powder and Suspension Dosage Form

Objective. To develop and compare HPLC-DAD and UHPLC-UV assays for the quantitation of posaconazole in bulk powder and suspension dosage form. Methods. Posaconazole linearity range was 5–50 μg/mL for both assays. For HPLC-DAD assay, samples were injected through Zorbax SB-C18 (4.6 × 250 mm, 5 μm) column. The gradient elution composed of the mobile phase acetonitrile: 15 mM potassium dihydrogen orthophosphate (30 : 70 to 80 : 20, linear over 7 minutes) pumped at 1.5 mL/min. For UHPLC-UV assay, samples were injected through Kinetex-C18 (2.1 × 50 mm, 1.3 μm) column. The mobile phase composed of acetonitrile: 15 mM potassium dihydrogen orthophosphate (45 : 55) pumped isocratically at 0.4 mL/min. Detection wavelength was 262 nm in both methods. Results. The run time was 11 and 3 minutes for HPLC-DAD and UHPLC-UV assays, respectively. Both assays were linear (r 2 > 0.999) with CV% and % error of the mean <3%. Limits of detection and quantitation were 0.82 and 2.73 μg/mL for HPLC-DAD and 1.04 and 3.16 μg/mL for UHPLC-UV, respectively. The methods quantitated PSZ in suspension dosage form with no observable interferences. Conclusions. Both assays were proven sensitive and selective according to ICH guidelines. UHPLC-UV assay exhibited some economic and chromatographic separation superiority.

Posaconazole, a prophylactic therapy in patients with haematological cancer: drug use evaluation study

Background Posaconazole (PSZ), is an antifungal prophylactic therapy that is used in haematological cancer patients. In 2010, PSZ was added to the formulary of the National Centre for Cancer Care & Research (NCCCR), the only adult cancer hospital in Qatar. Objective To conduct a drug use evaluation (DUE) study of PSZ at NCCCR. Method A retrospective, single centred, observational DUE study was conducted to include a convenient sample of haematological cancer patients who used PSZ prophylactically in 2010. All 31 patients were nominated; 20 patients profiles were reviewed. Data were collected using a pre-prepared collection sheet and descriptive analysis was performed. Results One patient was excluded as he was not a haematological cancer patient. All remaining 19 patients received PSZ for prophylaxis and were compliant. More than 50% of patients received proton pump inhibitors concurrently with PSZ. Only 1 case had a recorded recommendation regarding the administration of PSZ with food. Five patients received a vincristine based chemotherapy protocol, one of which developed seizures. Two patients developed mild breakthrough fungal infection while on PSZ. Conclusions The PSZ practice in NCCCR abides by its regulations of use. However, clear recommendations regarding administration of PSZ with meals is essential. PSZ co-administration with proton pump inhibitors should be either stopped or managed by PSZ therapeutic drug monitoring to avoid PSZ sub-therapeutic levels. Possible serious drug interactions in patients treated with vincristine based chemotherapy should be highlighted and monitored.

The effect of hyperlipidemia on the pharmacokinetics, hepatic and pulmonary uptake of posaconazole in rat

OBJECTIVES Posaconazole (PSZ), lipophilic antifungal drug, is used for prophylactic purposes in immunocompromised patients. Our aim is to study its pharmacokinetics and tissue distribution in different elevated lipoprotein levels in rat. METHODS To study PSZ pharmacokinetics and protein binding, rats (n=30) were assigned to three groups, normal lipidemic (NL), intermediate (IHL) and extreme hyperlipidemic (HL). Hyperlipidemia was induced by i.p. injection of (1g/kg) poloxamer 407 in rats. Serial blood samples were collected for 72h p.o. PSZ (40mg/kg). PSZ unbound fractions in NL, IHL and HL plasma were determined using ultrafiltration kits. To study tissue distribution, rats (n=64) were allocated into NL and HL groups. After p.o. administration of PSZ 40mg/kg, blood samples were collected, lungs and liver tissues were extracted over 72h. RESULTS Orally dosed rats showed two distinct Cmax peaks reflecting PSZ enterohepatic circulation. The incremental increase in lipoprotein levels have resulted in significant decrease in PSZ unbound fraction, a significant increase in Cmax1 and the AUC0-24h (NL=IHL<HL) and a significant decrease in PSZ terminal phase half-life (NL<IHL<HL). However, AUC0-∞ and weight normalized Cl/F were not significantly different among groups. The liver and lung PSZ uptake were decreased by hyperlipidemia resulting in lower Cmax, AUC0-8h and delayed Tmax values within those tissues. However, AUC0-72h was similar between NL and HL groups. CONCLUSION Poloxamer induced lipoprotein level elevation caused alterations in the PSZ pharmacokinetics and decreased its hepatic and pulmonary uptake. This raises few concerns about its activity and possible drug interactions as a prophylactic therapy in hyperlipidemic immunocompromised populations.

Novel cremochylomicrons for improved oral bioavailability of the antineoplastic phytomedicine berberine chloride: Optimization and pharmacokinetics

Berberine chloride (BER) is an antineoplastic phytomedicine that combat non-Hodgkin lymphoma. BER suffers from low oral bioavailability due to p-glycoprotein efflux and first-pass metabolism. Lymphatic drug targeting recently gained a profound attention due to circumventing hepatic first-pass metabolism and targeting lymph diseases. Therefore, novel BER-loaded cremochylomicrons were elaborated to mitigate BER drawbacks and enhance its lymphatic targeting and bioavailability. Optimized cremochylomicron was prepared with 2.5%w/v Cremophor El and 12.5% w/w berberine content. Promising in vitro characteristics (particle size = 175.6 nm and entrapment efficiency = 95.5%) were obtained. Lyophilized system showed high colloidal stability over 6 months. In addition in vivo pharmacokinetics study demonstrated significant enhancement (>2fold) in the rate and extent of absorption in cremochylomicron over free BER. Moreover, cremochylomicrons demonstrated in significant increase in mean residence time and volume of distribution with decreased intestinal drug clearance as a result of efflux inhibition. In another avenue, a significant reduction in BER absorption (43%) in presence of cycloheximide inhibitor was obtained confirming the lymphatic targeting ability of cremochylomicrons. In conclusion, berberine-loaded cremochylomicron could be considered as a promising nanoplatform for targeting lymphatic system and improving BER oral bioavailability with lower dose and side effects.

HPLC Methods for Quantitation of Exemestane–Luteolin and Exemestane–Resveratrol Mixtures in Nanoformulations

Two HPLC-DAD assays for the simultaneous quantitation of exemestane (EXE) and resveratrol (RES)-Mix 1-and EXE and luteolin (LUT)-Mix 2-in novel breast cancer therapy nanoformulations were developed. Calibration curves 15-30 µg/mL and samples were injected through an Inertsil ODS-3 (250 × 4.6 mm, 5 µm) column. The gradient elution for Mix 1 was methanol : 0.05% (v/v) acetic acid in water (60 : 40 to 80 : 20, linear over 2 min), and for Mix 2, it was methanol : water (60 : 40 for 4 min, then ramped linearly to 90 : 10, over 12 min) pumped at 1.5 mL/min for 4 min, then 1 mL/min till the end of run. EXE, RES, LUT and flutamide (internal standard (IS)) were measured at 246, 307, 350 and 300 nm, respectively. For Mix 1, RES, EXE and IS eluted at 3.5, 6.8 and 7.4 min, respectively, while for Mix 2, LUT, EXE and IS eluted at 7.5, 11.4 and 12.7 min, respectively. The mean r(2) for the standard curves was ≥0.99, and percentage coefficient of variation and % error of the mean were <2. Both assays successfully quantitated Mix 1 and Mix 2 in their nanoformulations. The two developed assays were sensitive and selective for the analysis of EXE-LUT and EXE-RES mixtures in nanoformulations according to International Conference on Harmonization guidelines.

Studying the knowledge, attitude and practice of antibiotic misuse among Alexandria population

Aim To assess knowledge, attitude and practice (KAP) of antimicrobial self-medication among a convenience sample of population in Alexandria, Egypt. Methodology A descriptive cross-sectional study using a self-administrated semi-constructed questionnaire. A convenience sample of 359 participants was studied using appropriate consent. The questionnaire had four sections: demographics, KAP, professional medical knowledge and attitude of children caregivers toward antimicrobial self-medication. The questionnaire was initially constructed in English and then translated into its final Arabic version. The Arabic version was pilot-tested and face-validated. Descriptive and quantitative analysis were performed using SPSS (V.20.0). Results Approximately 64% (231) of the studied population used antibiotics without prescription in the past 12 months. This was significantly correlated with female gender and lack of knowledge. The main reason for self-medication was due to saving time and effort (109, 47%) followed by not preferring doctor visits (89, 39%). More than 60% of cases used amoxicillin-clavulanic acid. The main sources of antibiotics were leftovers from previously prescribed pharmaceuticals and those purchased from community pharmacies. 85 participants were young children caregivers of which 18 (21%) reported administering antibiotics to their children without consulting a physician. Out of 115 who claimed attaining medical background, only 30 (26%) managed to answer section 3 correctly with 23 of them reporting antibiotic self-medication. Conclusion This study showed an increased tendency towards antibiotic self-medication among Alexandrian adults and children that was not significantly decreased in population with medical background. The reasons discussed within the study should be further addressed to decrease such practice.