Assessment of Pharmaceutical Equivalence: Difference Test or Equivalence Test?

Pharmaceutical equivalence is an important step towards the confirmation of similarity and interchangeability among pharmaceutical products, particularly regarding those that will not be tested for bioequivalence. The aim of this paper is to compare traditional difference testing to two one-side equivalence tests in the assessment of pharmaceutical equivalence, by means of equivalence studies between similar, generic and reference products of acyclovir cream, atropine sulfate injection, meropenem for injection, and metronidazole injection. All tests were performed in accordance with the Brazilian Pharmacopeia or the United States Pharmacopeia. All four possible combinations of results arise in these comparisons of difference testing and equivalence testing. Most of the former did not show significant difference, whereas the latter presented similarity. We concluded that equivalence testing is more appropriate than difference testing, what can make it a useful tool to assess pharmaceutical equivalence in products that will not be tested for bioequivalence.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Permeation of large antineoplastics into wild strain of Saccharomyces cerevisiae

he Ames Test approach. However the cell permeability of yeast has been considered a limitant factor to this kind of assay and many researchers have been introducing genetic modifications into wild strains to improve the sensitivity to chemical compounds. In our study, we used Saccharomyces cerevisiae ATCC 9763, well known and very common strain in antibiotic assays, and we evaluated the cytotoxicity of some antineoplastic agents (etoposide, epirubicin, carboplatin, cisplatin and mitoxantrone). Each culture was observed under the light of microscope and photographed. Neither genetic modification nor addition of permeation inducers, as dimethylsulfoxide (DMSO), were introduced during the assays and the cells presented good sensitivity to those compounds, demonstrating that other potential strains and characteristics of cells should be reconsidered to improve these assays apart from the cellular permeability.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Microbiological assay for apramycin soluble powder

The aim of this study was to validate an agar diffusion method through the parameters linearity, precision and accuracy, to quantify apramycin in soluble powder. The calibration curve of apramycin was constructed by plotting log of concentrations (µg ml-1) versus zone diameter (mm) and shows good linearity in the range of 1.0-4.0 µg ml-1. The precision of the assay was determined by assaying samples at the same day (repeatability - R.S.D. = 2.00%) and on different days (intermediate precision - R.S.D. = 5.06%) and indicate good precision. The accuracy expresses the agreement between the accepted value and the value found. The mean recovery was found to be 100.49 % for apramycin soluble powder. The results indicated that the microbiological assay proposed in this work hold linearity, precision and accuracy being an acceptable alternative method for routine quality control of apramycin in the pharmaceutical dosage form studied.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Chitosan nanogels for biomedical applications: choosing a suitable sterilization method

Poster presented at the 10th World Biomaterials Congress. Montreal, Canada, 17-22 May 2016N/

Evaluation of cisplatin, doxorubicin and paclitaxel inactivation using asepto 75^TM 0.5 %, sodium hypochloride 10 % and sodium thiosulfate 10 % by high performance liquid chromatography (HPLC) and in vitro cytotoxicity test

Antineoplastic agents are considered risk drugs; that is, they can cause harmful effects, such as genotoxicity, carcinogenicity, teratogenicity, as well as fertility alterations, therefore being the exposure of health professionals to these substances considerably worrying. These medicaments must be submitted to physical, chemical and biological analyses, what generates a considerable volume of residues, what also requires treatment. The aim of this work was to evaluate the efficacy of different methods of inactivation concerning cisplatin, doxorubicin and paclitaxel, using high performance liquid chromatography and in vitro cytotoxicity test. The results demonstrated that Asepto 75TM is efficient for chemical and biological inactivation of the three drugs, being the exposure time determinant for cisplatin chemical degradation. Cytotoxicity levels varied from none to slight. In spite of its own degree of cytotoxicity, sodium hypochloride was also effective in the chemical inactivation of the three drugs. Sodium thiosulfate degrader, however, was only effective concerning cisplatin chemical inactivation, presenting no effect on doxorubicin or paclitaxel. The results of the in vitro tests were compatible with those from the chemical evaluation. It can therefore be concluded that the inactivation of cytotoxic drugs prior to waste effectively reduces occupational and environmental risks.Colegio de Farmacéuticos de la Provincia de Buenos Aire

About the sterilization of chitosan hydrogel nanoparticles

In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP) associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility) with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS) hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation), a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP) hydrogel nanoparticles (CS-HNP), with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol). Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles.info:eu-repo/semantics/publishedVersio

Nanocarriers: more than tour de force for thymoquinone

Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers

Evaluation of Microbicidal Activity of Oxygen-Containing Plasmas using Biological Monitors with Different Lumen Calibers

New technologies and sterilization agents for heat-sensitive materials are under intense investigation. Plasma sterilization, an atoxic low-temperature substitute for conventional sterilization, uses various gases that are activated by an electrical discharge, generating reactive species that promote lethality in microorganisms. Here, assays were performed using pure O2 and O2 + H2O2 mixture gas plasmas against a standard load of Bacillus atrophaeus spores inoculated on glass carriers inside PVC catheters. The sterilization efficiency was studied as a function of plasma system (reactive ion etching or inductively coupled plasma), biological monitor lumen diameter, gas, radio frequency power, and sub-lethal exposition time. After sterilization, the biological monitors were disassembled and the surviving bacteria were grown in trypticase soy broth using the most probable number technique. Plasma antimicrobial activity depended on the catheter’s internal diameter and radio frequency powers. The O2 + H2O2 mixture exhibited higher microbial efficacy than pure O2 in both plasma systems.Colegio de Farmacéuticos de la Provincia de Buenos Aire