M Draoui

REVIEW: FROM SCREENING TO APPLICATION OF MOROCCAN DYEING PLANTS: CHEMICAL GROUPS AND BOTANICAL DISTRIBUTION

Many dyes are contained in plants and are used for coloring a medium. They are characterized by their content of dyes molecules. They stimulate interest because they are part of a sustainable development approach. There are several chemicals families of plant dye which are contained in more than 450 plants known around the world. In this article, a study based on literature allowed us to realize an inventory of the main dyes plants potentially present in Morocco. A list of 117 plants was established specifying their botanical families, chemical Composition, Colors and parts of the plant used. Keywords: Natural dye, Morocco, Chemical structures, Plant pigments, Extraction

Inventory of Toxic Plants in Morocco: An Overview of the Botanical, Biogeography, and Phytochemistry Studies

Since they are natural, plants are wrongly considered nondangerous; therefore people used them in various contexts. Each plant is used alone or in mixture with others, where knowledge and the requirements of preparation and consumption are not mastered. Thus, intoxications due to the use of plants have become more and more frequent. The reports of intoxications made at the Antipoison Center and Pharmacovigilance of Morocco (ACPM) support this finding, since the interrogations suffered by the victims show that the use of plants is practiced irrationally, anarchically, and uncontrollably. Faced by the increase of these cases of poisoning in Morocco, it seemed necessary to investigate the nature of poisonous plants, their monographs, and the chemicals responsible for this toxicity.

Interactions between injectable anticancer drugs and polyvinyl chloride bags: Evaluation of the adsorption phenomenon after reconstitution

Introduction During the reconstitution of a drug and during its storage, there are risks of interactions between the drug and the bag used for the preparation. Polyvinyl chloride is a material used in the manufacture of a large part of chemotherapy infusion bags. It is subject to many interactions like sorption of drugs and release of phthalate additives. Material and Methods Seven anticancer drugs used in pediatric oncology were involved in our study. After reconstitution of the anticancer agents in polyvinyl chloride bags, the adsorption phenomenon between the container and the contents is evaluated by infrared spectroscopy by analyzing the inner surface of the polyvinyl chloride. Subsequently, for the anticancer agents which exhibited an adsorption–container–content, the analysis was carried out by ultraviolet–visible spectrophotometry in order to examine the kinetics of the concentration of reconstituted anticancer drugs. Results All the polyvinyl chloride bags gave a spectrum identical to the spectrum of the reference bag, except the bags used to reconstitute etoposide whose spectra showed 12 additional peaks. With the absorbances measured by ultraviolet–visible spectrophotometry at different times, the analysis of variance statistical analysis shows that there is a significant difference in absorbances between t0 and all the other measurement times. Conclusion This study testifies to the existence of a container–content interaction between etoposide and polyvinyl chloride. Thus, reconstitution of etoposide for intravenous infusion into a polyvinyl chloride bag should be used immediately. For etoposide preparations intended for storage beyond 24 h, it is recommended to use a container other than the polyvinyl chloride bag.

3PC-010 Chemical interactions between antibiotics and cations administered by injection

Background Simultaneous administration of drugs is a common gesture in different care units. This gesture may be causing some major complications for patients. In 1996, serious accidents in premature or newborns concomitantly treated with ceftriaxone and intravenous calcium gluconate were reported in France. In 2002, a death was reported in a newborn after administration of calcium gluconate plus ceftriaxone despite the difference in routes of drugs administration and the difference in time of injection. Purpose We tried to study the different physicochemical interactions that some antibiotics might have with cationic ions used in injectable form in hospital.Abstract 3PC-010 Table 1 Antibiotic Ca2+ Mg2+ Fe2+ Gentamicin 80 mg/2 mL * NP NP Flucloxacillin 1 g/2 mL 2.44 10–3 2.58 10–3 5.29 10–7 Amoxicillin+Clavulanic acid 500 mg/62. 5 mL NP NP ** Ceftriaxone 1 g/2 mL 7.93 10–4 7.94 10–3 1.32 10–3 Ceftazidime 1 g/2 mL NP NP 1.79 10–3 Colistin 1000000 IU NP NP NP Ampicillin+Sulbactam 1 g/500 mg NP NP ** Levofloxacin 500 mg/100 mL NP NP NP Teicoplanin 400 mg/2 mL NP NP NP Piperacillin+Tazobactam 4 g/500 mg NP NP ** Ertapenem 1 g/2 mL NP NP 5.10 10–4 Imipenem 500 mg NP NP ** NP: not precipitate. *:precipitation is caused by the salt of the antibiotic (sulphate). **:there is a precipitate but we do not know the antibiotic that is the cause. Material and methods We have selected the most consumed antibiotics in our university hospital and we tested them with bivalent cations commonly consumed in care services. The evaluation of the nature of the mixture was made using the solubility product of the melange of antibiotic and cation. We mix 0.5 mL of each cation solution concentrated to 5% and 0.5 mL of each antibiotic solution. Results The solubility product expressed in (mol/l)2 of the melange of each antibiotic with each cation are summarised in the table below: Conclusion Knowledge of drug interactions is essential for a better use of these drugs in hospital. Interactions of certain antibiotics commonly used with bivalent cations can lead to some precipitates undetected by nurses who administer the injectable treatments, which could cause serious accidents during the simultaneous use in patients. The summary of product characteristics of these antibiotics should incorporate these interactions to avoid those unforeseen accidents. References and/or Acknowledgements Acknowledgements to analytical chemistry team. No conflict of interest

3PC-034 Screening for physicochemical incompatibilities of cytotoxic drugs after reconstitution: the case of methotrexate

Background Physicochemical incompatibilities of parenteral drugs cause several problems in hospital practice. These incompatibilities can be represented by precipitation, complexation or colour change before or during administration to patients. Understanding these incompatibilities allow pharmacists to avoid many problems during preparation and administration. Purpose To determine physicochemical incompatibilities of a cytotoxic drug widely used in paediatric oncology (methotrexate) with certain trace elements existing in food and medicines, as well as in food supplements. Material and methods We performed several mixtures to study physicochemical reactions between methotrexate reconstituted in infusion bags (25 mg/ml) and five cations: calcium (Ca2+), copper (Cu2+), iron (bivalent and trivalent), magnesium (Mg2+) and zinc (Zn2+). An interaction was elucidated by formation of a precipitate visible to the naked eye. Infrared spectroscopy was the method of authentication of precipitates. Results Precipitates were formed with the copper, zinc, bivalent and trivalent iron. On the other hand, there was no precipitate with calcium and magnesium. Functional analysis of infrared spectra of precipitates showed the presence of methotrexate. Conclusion The study of the physicochemical incompatibilities of methotrexate can avoid possible interactions with medicines, food or nutritional supplements containing trace elements. Recording to the results, methotrexate precipitates in the presence of copper, zinc and iron ions. The absence of the precipitate or change of colour in the other mixtures does not exclude a possible complexation. Reference and/or Acknowledgements 1. Benaji B, et al. Compatibility study of methotrexate with PVC bags after repackaging into two types of infusion admixtures. Int J Pharma1994;105(1):83–87. No conflict of interest

3PC-031 The influence of dead volume on reconstitution of injectable drugs

Background Parenteral drug administration plays an important role in hospitals. It is well known that a certain amount of a drug remains at the end of the infusion and is not administered to the patient because of the dead volume: this dead volume could be the origin of an underdosing. Purpose The aim of this study is to determine the dead volume of the injectable delivery system including the serum bag, perfusion tubulure, syringe and short catheter used for the reconstitution and administration of injectable drugs, and its impact on variation of the prepared doses. Material and methods We weighed, using an analytical balance, all the medical devices (serum bag, perfusion tubulure, syringe and short catheter) used in the administration of an injectable drug before and after the passage of an antibiotic solution. We can thus determine the dead volume remaining in each material. Statistical analysis were performed with SPSS 13. 0. Results The table shows that the dead volume differed between medical devices (p<0.001). It was significant for the serum bag and perfusion tubulure, and low for syringes and short catheters. The overall dead volume is estimated at 4.5±1.7 mL.Abstract 3PC-031 Table 1 Medical device Dead volume mean± SD (mL) (n =30 ) Serum bag 2.61±1.71 Syringe 2.5 mL 0.06±0.003 Syringe 5 mL 0.07±0.003 Syringe 10 mL 0. 07±0. 003 Syringe 50 mL 0.09±0.003 Perfusion tubulure 1.74±0.02 Short catheter G22 0.01±0.001 Short catheter G24 0.01±0.003 Conclusion A considerable amount of the infusion volume, and therefore of the antibiotic, depending on the concentration, is lost at the end of the infusion due to the dead volume depending on the medical devices used as demonstrated in this study and in other studies.1 Loss of a potential amount of a drug can constitute a problem regarding safety and efficacy of therapy, especially for drugs with narrow therapeutic margins. This is especially important for the serum bag and perfusion tubulure, where the dead volume is about 2.61 mL and 1.74 mL respectively. References and/or Acknowledgements 1. Cheikh A, Rhali Y, Mefetah H, Sbai I, Mojemmi B, Draoui M, Bouatia M. The influence of the dead volume of the closed system (spike–connector–syringe) on the reconstitution of injectable drugs. Eur J Hosp Pharm24(1):A214–A216. No conflict of interest

3PC-033 In vitro physicochemical interactions study between iron and anticancer drugs administrated in hospital

Background Iron is used like a medicine to treat or prevent haemolytic anaemia. When iron is administered concomitantly with certain drugs, it can change absorption of these drugs by complex reaction. Consequently, treatments become ineffective. Purpose To study in vitro physicochemical behaviour of iron with different cytotoxic drugs used in oncology therapeutic protocols. Material and methods We prepared several mixtures of bivalent and trivalent iron solutions with 13 anticancer drugs after their reconstitution. We mixed 0.1 ml of 5% iron solution (Fe 2+or Fe3+) with 1 mL of diluted drugs in glass tubes, and we observed in the presence or absence of a precipitate. The formed precipitates were washed, dried and identified by infrared spectroscopy and UV-visible spectroscopy. Spectra obtained are compared with those of the anticancer drugs studied. Results Results are represented in the following table:Abstract 3PC-033 Table 1 Cytotoxic drug (1 ml ) Interaction with iron Cytotoxic drug (1 ml ) Interaction with iron Fe 2+ (0.1 ml) Fe3+ (0.1 ml) Fe2+ (0.1 ml) Fe3+ (0.1 ml) Etoposide + Red Doxorubicin/Epirubicin black + Carboplatin – Yellow Vincristine – – Cyclophosphamide – Yellow Ifosfamid – Yellow Cytarabine + Red Cisplatin – Yellow Vinblastine – Yellow Methotrexate + + Dacarbazine – Yellow Bleomycin – – +: presence of precipitate –: no precipitate Spectra obtained by UV-visible and IR spectroscopy of the precipitates correspond to the spectra of cytotoxic drugs. We can deduce that the iron complex is incompatible with etoposide, cytarabin, doxorubicin, epirubicin and methotrexate. Conclusion The findings suggest that iron (Fe3 +and Fe2+) is not compatible with etoposide, cytarabine doxorubicin, epirubicin, and methotrexate. We can deduce that intravenous iron should preferably be taken at least 2 hours before or 2 hours after taking these anticancer drugs to limit the risk of developing complications. For oral formulae like etoposide and methotrexate, concomitant administration of oral iron should be avoided in order to ensure good absorption. References and/or Acknowledgements 1. Arlet J-B, et al. Iron therapy: indications, limitations and modality. Rev Méd Int2012;34:26–31. 2. Dan L Longo MD. Iron-deficiency anaemia. N Engl J Med2015;372:1832–43. No conflict of interest

3PC-009 Physicochemical stability of intravenous injection of a generic product of furosemide prepared in polypropylene syringes

Background Furosemide is a diuretic widely indicated in paediatric diseases especially for the treatment of oedema associated with congestive heart failure, cirrhosis of the liver or renal disease. Its stability is very important and must be proved to ensure paediatric patient safety. Purpose The aim of this study was to determine the physicochemical stability for furosemide 1 mg/ml in polypropylene syringes stored in different conditions. Material and methods Nine polypropylene syringes were prepared using the generic product of furosemide (1 mg/ml) in NaCl 0.9%. The nine syringes were stored in different conditions for 72 hours. The following table describes these conditions:Abstract 3PC-009 Table 1 Number of syringes of furosemide 1 mg/ml 3 3 3 Temperature 25°C±3°C 8°C±3°C 25°C±3°C Light Daylight Absent Artificial We studied several physical and chemical parameters immediately after preparation (0 hour) and after 6, 24, 48 and 72 hours. These parameters are colour, opacity, presence of precipitation or microagregate, pH and absorbance. Each preparation was visually inspected in front of a black and white background. Preparations were centrifuged and aliquots were examined by microscope. pH measurements were carried out by pH-metre and spectrophotometric measurements were obtained after dilution of solutions, at three wavelengths: 229, 278 and 331 nm with a UV-visible spectrophotometer. Results After 72 hours, no colour change, no opacity, no precipitation and no microaggregate were observed. For chemical parameters, there was no variation in pH absorbance in all conditions of storage. For spectrophotometric measurements, there is no significant change in absorbance in all conditions of storage. Studies showed that degradation products do not absorb at the same wavelengths of furosemide. We can deduce that the method used is specific for the determination of furosemide. Conclusion Furosemide 1 mg/ml in NaCl 0.9% propylene syringes preserved its physical and chemical properties for at least 72 hours in all conditions of storage. So we can prepare many paediatric injections in our hospital that we can store for 72 hours. References and/or Acknowledgements 1. HansBundgaard, et al. Photodegradation and hydrolysis of furosemide and furosemide esters in aqueous solutions. Int J Pharma, 1988; 42: 217–224. No conflict of interest

PP-030 The influence of the dead volume of the closed system (spike–connector–syringe) on the reconstitution of injectable drugs

Background The closed system is designed, first, to protect patients and clinicians against exposure to hazardous drugs during the preparation of cytotoxic drugs and secondly, to protect the drugs against any exposure to external microbiological and physical contaminants. Purpose The aim of this study was to determine the dead volume of spike–connector–syringe system used for the reconstitution of cytotoxic drugs and its impact on the variation of prepared doses. Material and methods The spike, connector and syringe (10 or 20 mL) were weighed using an analytical balance before and after passing a solution of distilled water. Taking into account the density of water, we can thus determine the dead volume remaining in every material. For each measurement, the test was performed 30 times for each medical device. Results The table shows that the dead volumes were different for the three devices: spike, connector and syringes (p<0.001). There was no significant differences between the dead volumes of the two syringes tested (10 and 20 mL) (p> 0.05). Dead volume Vial adapter (spike) Connector Syringe 10 mL Syringe 20 mL Mean (mL) 0.1192 0.2043 0.0702 0.0596 Conclusion Reconstitution of cytotoxic drugs is influenced by several factors, some of which are controllable and others are unpredictable. The dead volumes can cause overdose or underdose, especially for preparations of low volume and expensive drugs. This phenomenon is important for connectors and spikes where the dead volume is about 0.2 mL and 0.1 mL, respectively. For syringes, the dead volume is not very important and does not vary with the volume of the syringe. This study showed that we must take into account the dead volume on reconstitution of cytotoxic drugs. Thus it would be highly advisable to use connectors whose dead volume is negligible compared with the prepared final volume. References and/or acknowledgements Acknowledgements to the analytical chemistry team. No conflict of interest

DI-071 In vitro comparison of antacid drugs: Application to six marketed formulations

Background Antacids are intended to neutralise the gastric H+ ions without interfering with the secretory process. They are generally administered 1 h 30 min after the beginning of a meal. Given the multitude of antacids on the market, it would be interesting to have quantitative techniques to compare these products and to demonstrate their physiological behaviour. Purpose To evaluate the behaviour of antacids in the presence of an increasing amount of acidity in vitro and to predict their use depending on the importance and periodicity of gastric acidity in vivo. Material and methods We studied the in vitro behaviour of six antacid drugs. For this, a therapeutic dose was diluted in 100 ml of distilled water, to which were added increasing amounts of 0.1 N HCl in increments of 0.2 ml every 30 s up to a total acid volume of 25 ml. The variation in pH of the mixture was followed by pH-metry. Each test was repeated three times. The composition of the studied antacids is shown in table 1.Abstract DI-071 Table 1 Drug A For 100 ml of oral suspension:-Aluminium hydroxide (3.49 mg)-Magnesium hydroxide (3.99 mg) Drug B For a 20 g sachet of oral suspension:-Aluminum phosphate gel at 20% (12.38 g)-Magnesium oxide (152 mg) Drug C For a 20 g sachet of oral suspension:-Colloidal aluminum phosphate at 17% (14.4 g) Drug D For a 10 ml sachet of oral suspension:-Aluminium alginate (500 mg)-Sodium bicarbonate (267 mg) Drug E For one effervescent tablet:-Sodium bicarbonate (170 mg)-Sodium sulfate (285 mg)-Sodium dihydrogen phosphate (195 mg) Drug F For one suckable tablet:-Calcium carbonate (680 mg)-Magnesium carbonate (80 mg) Results The in vitro behaviour of the six antacid drugs in the presence of increasing amounts of 0.1 N HCl is represented in figure 1.Abstract DI-071 Figure 1 Conclusion The proposed method allowed us to quantitatively compare the studied antacids. According to the results, drug C slightly neutralised stomach acid without an extended effect. It can be prescribed for low and temporary gastric acidity. Drugs A, B and F had an average and extended neutralising action (pH stabilisation around 5). They can be prescribed for moderate and prolonged gastric acidity. Regarding drugs D and E which had a strong neutralising and long acting action that stabilised the pH around 7.5, they can be prescribed for high and prolonged gastric acidity. No conflict of interest.