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FORENSIC SCIENCE Reactions ShareShare onFacebookTwitterWechatLinked InRedditEmail C&EN, 2023, 101 (16), p 3May 22, 2023Cite this:C&EN 101, 16, 3Letters to the editorPortable spectrometers’ implications for court casesAs a defense lawyer in Toronto, I read with interest “Portable Spectrometers Give On-Site Testing a Boost,” by Carolyn Wilke (C&EN, April 17/24, 2023, page 28). These new, often handheld, devices may well be better than the more traditional color tests or wet-chemistry kits. But the article doesn’t go into detail about the important distinction between these valuable law enforcement investigative tools and eventual proof in court to convince a judge for the criminal law requirement of beyond a reasonable doubt.And it would appear that neither these new devices nor the color tests measure quantity, which may be important for eventual court determination of guilt and sentencing.In Canadian law, there is another, more problematic concern, for which these new devices would not help. It is apparent government policy and practice to not reveal the science behind drug determinations. There is no proper scientific report. For years, qualitative disclosure has effectively been prevented with Controlled Drugs and Substances Act s. 51. More recently, disclosure of the science behind quantitative measurements has simply been declined by Crown counsel.This is a matter of both science policy and justice:▸ Unexplained science is bad science—for that reason alone.▸ Nondisclosure by the Canadian federal government strikes at the heart of the concepts of justice. This is perhaps especially important for police stings wherein the target may be an individual with addiction or other disadvantages trading in small quantities of drug—in serious jeopardy for significant jail time.Perhaps of greatest concern is that hardly any of the personnel of the Canadian legal system would seem to be concerned with these problems of science policy and justice. Or concerned that the Controlled Drugs and Substances Act s. 51 remains as law. And perhaps the coming availability of the new devices would falsely allay that there are serious problems of scientific and legal principle.Michael GrossmanTorontoIndustry membershipWhen I read in your editorial in the April 10 issue about the decline in American Chemical Society industry memberships (page 2), a possible explanation was given in the same place. “As a businessperson, Rothrock doesn’t get as much out of ACS meetings as she once did.”I work in industrial R&D and attended the ACS Spring meeting in Indianapolis. It is very obvious that these meetings are heavily focused on academics. Companies send representatives to many other more industry-focused conferences and trade shows and don’t see the value of an academia-heavy additional conference. But in industrial conferences, companies don’t share details of the chemistry they are doing with others—obviously. And this is exactly the advantage of ACS meetings: most chemistry is openly shared and discussed. I saw this as a great opportunity to get ideas and inspiration for my work projects in industry, even though we are actually working on entirely different things than what was shown at the ACS meeting. However, you know what you work on and check out related chemistry shown in talks and posters. Students and professors happily discuss their work with you. And the combined costs of ACS membership and conference registration are far less than the fees typically paid at many industrial conferences.It may depend on what you do in industry. But companies should realize that attending ACS meetings and being a member can add a lot of value to them as well.Martin GloddePine Brook, New JerseySlogan for ACSAfter reading Donna Peterson’s letter in the May 1 issue of C&EN (page 3), I propose that all readers of this quality publication help further craft an American Chemical Society slogan that might catch public attention. My suggestions would be “Chemistry for better living on a better planet!” or “Better living on a better planet through chemistry!”Thomas Andrew RungeRichland, Michigan CorrectionsMay 1, 2023, page 8: The news story about a partnership between Gevo and LG Chem to develop technology for biobased propylene misstates the product LG Chem plans to make. LG wants to use biobased propylene to make chemicals, not sustainable aviation fuel and renewable diesel.May 8, 2023, page 3: The news article on GSK’s respiratory syncytial virus vaccine gives an incorrect title for Andrew McConaghie. He is a senior writer, not analyst, at Citeline.

Improved uptake and bioavailability of cinnamaldehyde via solid lipid nanoparticles for oral delivery

Objective The purpose of this experiment was to explore the effect of Solid lipid nanoparticles (SLNs) on improving the oral absorption and bioavailability of cinnamaldehyde (CA). Methods CA-SLNs were prepared by high-pressure homogenization and characterized by particle size, entrapment efficiency, and morphology, thermal behavior and attenuated total reflection Fourier transform infrared (ATR-FTIR). In vitro characteristics of release, stability experiments, cytotoxicity, uptake and transport across Caco-2 cell monolayer of CA-SLNs were studied as well. In addition, CA-SLNs underwent pharmacokinetic and gastrointestinal mucosal irritation studies in rats. Results CA-SLNs exhibited a spherical shape with a particle size of 44.57 ± 0.27 nm, zeta potential of −27.66 ± 1.9 mV and entrapment efficiency of 83.63% ± 2.16%. Differential scanning calorimetry (DSC) and ATR-FTIR confirmed that CA was well encapsulated. In vitro release of CA-SLNs displayed that most of the drug (90.77% ± 5%) was released in the phosphate buffer, and only a small amount of drug (18.55% ± 5%) was released in the HCl buffer. CA-SLNs were taken up by an energy-dependent, endocytic mechanism mediated by caveolae mediated endocytosis across Caco-2 cells. The CA permeation through Caco-2 cell was facilitated by CA-SLNs. The outcome of the gastrointestinal irritation test demonstrated that CA-SLNs had no irritation to the rats’ intestines. Compared with CA dispersions, incorporation of SLNs increased the oral bioavailability of CA more than 1.69-fold. Conclusions It was concluded that CA-SLNs improved the absorption across Caco-2 cell model and improved the oral administration bioavailability of CA in rats.

Cyclosporine and Pentoxifylline laden tailored niosomes for the effective management of psoriasis: In-vitro optimization, Ex-vivo and animal study

Psoriasis is a chronic skin inflammatory auto-immune disorder. Cyclosporine is the drug of choice in severe cases of psoriasis for systemic administration. But its systemic administration leads to some serious side effects like nephrotoxicity and cardiovascular disorders. Pentoxifylline is reported to reduce such side effects of cyclosporine and also it is found useful in the management of psoriasis. In this study, Box-Behnken design was used to prepare and optimize Cyclosporine and Pentoxifylline loaded niosomes. The optimized niosomes were prepared using cholesterol and surfactant (7:3), a total of 500 µmol. Ratio of Tween 80 to span 80 for the preparation of optimized niosome was 0.503 (tween80:span80), and hydration and sonication time were kept at 60 min and 10 min, respectively. Size, Poly Dispersity Index, zeta potential, and % entrapment efficiency of Pentoxifylline and cyclosporine, for optimized niosomes were found to be 179 nm, 0.285, −37.5 mV, 84.6%, and 75.3%, respectively. The optimized niosomes were further studied for in-vitro skin permeation and skin deposition. Though niosomes significantly influenced the permeation of both drugs, only a small amount of drug (both cyclosporine and Pentoxifylline) was permeated through the skin. In comparison with the permeation, the quantity of drug retained in the stratum corneum and viable epidermis (SC and VED) was very high. In the in-vivo studies conducted on mice induced with psoriasis using imiquimod, both the histopathology and psoriasis area severity index has shown marked improvement in the skin condition of mice treated with niosomes loaded with Pentoxifylline and cyclosporine, in comparison with the solution/suspension of individual drugs. The study shows that niosomes could be effectively used for the simultaneous delivery of cyclosporine and Pentoxifylline for the better management of psoriasis.

Detection Measurements of Some Drugs Materials in Fingerprints

The major goal of this project is to use the Gas Chromatography–Mass Spectrometry (GC-MS) instrument to evaluate the fingerprints of illicit amphetamine. Samples of amphetamine were obtained from the Iraqi Narcotics Control Bureau. The fingerprints were examined before and after contamination with anesthetic powder. The results showed a clear difference between the spectrum of the pure fingerprint and the spectrum of the contaminated fingerprint with amphetamine. The highest peak of the drug sample was recorded at the time (6.80) minutes and Abundance 120000, and in contrast the appearance of the same peak in the fingerprint sample at the time (6.80) and Abundance 120000, and thus we find that the (GC-MS) device is sensitive for a small amount of drugs and can be used to detect it in the fingerprints.

Formulation, Development and Characterization of Sustained Release Formulation of Herbal Extracts

Aim: The aim of the present investigation is to design of sustained release dosage form of different extracts that will help in releasing only small quantities of drug over a prolonged period of time. Material and Methods: The different ingredients for formulations are given as in Table 1 below. The measured quantities of drug, HPMC, MCC and NaHCO3 were mixed thoroughly using a mortar and pistil. The granules were punched into tablets using direct compression technique. The blank formulation (or) placebo (HPMC+ MCC+NaHCO3) and polyherbal formulation were also tested using FTIR Spectrometer. The release rate kinetics of the formulations was analyzed and the data obtained were fitted into Zero order, First order, Higuchi model and Kozmeyer Peppas model. Results: The pre-formulation study results obtained on various parameters on granules were found satisfactory. The granules obtained for the batches (F1-F12) were satisfactory. No rat holing, capping or sticking was observed during the flow of granules from the hopper. The maximum weight variation of the tablets was±1.8%, which falls within the acceptable range of±5%, hence the tablets passed the weight variation test. Hardness for tablets of all batches was in the range of 4.92 to 5.35 kg/cm², which falls above the limit of not less than 3.0 kg/cm². The floating lag time ranged from 35 s to 50 s. From the Table 5, it was found that the formulation F11 has the minimum floating lag time of 35 s and maximum total floating time of 15 h with 100.12% drug content. Conclusion: The effect of ingredients in the polyherbal tablet was analyzed, where HPMC contributed as the floating matrix, MCC to increase the bulk density of the tablet and sodium bicarbonate to initiate the dissolution process.

Evaluation of Iran's pharmaceutical policies in the import of drugs and determining the nature of imported drugs using the ABC-VED Method

Background: The supply of medicines in every country is vital in any country, and access to appropriate medicines ensures the health of that community by preventingthe spread of smuggling. The present study aimed to evaluate the current policies of Iran to supply medicines through importation and examine the application of the ABC-VED (Always, Better, Control-Vital, Essential, Desirable) method in assisting policymakers in making decisions on the medicine importation. Method: The present research study was conducted in qualitative and quantitative phases. In the qualitative phase, face-to-face interviews were conducted with 13 health experts in the field of production and import of medicine and their "content analysis" was done using MaxQDA 18 software.In the quantitative phase, to determine the nature of imported drug items, the ABC-VED analysis matrix and the information available in the pharmaceutical statistics of 2019 were used. Then, the distribution of drugs in each of the matrix categories was determined. Result: In the qualitative phase of the study, experts pointed to the impact of restrictive policies on importation of medicines, reducing access to medicines, increasing smuggling, reducing innovation, weakening marketing, and reducing the quality and increasing price of domestically produced medicines. In the quantitative phase, it was found that AV category consists of 36, AE 145, AD 85, BV 31, BE 240, CV 126, CE 970, and CD 672 type of medicines using the ABC-VED matrix. Finally, 21.5 % of medicines were categorized in group I belonging to vital and expensive medicines, 7.2 % in group II that are essential medicnies with moderate prices, and finaly 1 % were categorized in group III which are desirable medicines with lower prices. Conclusion: According to the opinions of experts in the country pharmaceutical industry, Iran's policy on drug importations has always been contractionary. Although it has led to lower prices and increased patients' access to medicines, it made side effects on the pharmaceutical system. Thses side effects includ sectional medical shortages over time. Policymakers can restrict the import of expensive and small quantities of drugs and allocate more funds to the supply of vital drugs. The analyses used cannot be the criterion for decision alone and can only indicate drug priorities in budget shortages and must make decisions within a multi-criteria decision framework.

Proof-of-concept for a miniaturized shake-flask biopharmaceutical solubility determination by sonic mixing.

The solvent volume must be very small to obtain biopharmaceutically relevant drug solubility data with low consumption of the solid sample which is often in low supply during early drug development. However, the adequate and repeatable mixing of a small volume can be challenging. We therefore developed a straightforward technique based on the shake-flask method which employed only sonication for mixing a very small amount of drug in an aqueous solvent at a stable pH and temperature. To test the technique, the solubilities of the model compounds carvedilol, digoxin, propranolol, theophylline, and verapamil were determined. The determined solubility values agreed well with the conventional shake-flask solubility data obtained in our laboratory and previously published literature data. The time necessary for the measurements (24 h), was shown to be similar to the conventional shake-flask method even for the low solubility drugs digoxin and carvedilol. The solubility - pH dependence can be established very well as shown with verapamil and propranolol and confirmed with a pH in-dependent solubility of theophylline.

Caracterização do crime de tráfico de drogas a partir das sentenças condenatórias da Vara de combate ao crime organizado de Belém-PA

O artigo visa caracterizar do crime de tráfico de drogas por meio do estudo das sentenças condenatórias da Vara de Combate ao Crime Organizado em Belém-Pará-Brasil. Mostra-se importante para analisar como a Lei Nº 11.343/2006, que instituiu o Sistema Nacional de Políticas Públicas sobre Drogas, tem sido aplicada em casos reais. A técnica estatística como metodologia, a partir de tabelas e gráficos para visualização dos resultados. O marco teórico é a criminologia crítica, momento em que se reflete sobre a seletividade do sistema penal, por meio da qual se busca entender as razões da escolha do estereótipo de determinadas pessoas para serem criminalizadas pelo sistema de justiça criminal. Percebe-se que, na maioria das vezes, a condenação ocorre em razão do tráfico de pequenas quantidades de droga e por condutas típicas que poderiam configurar tanto tráfico de drogas como porte de drogas para uso pessoal, demonstrando a existência de um estereótipo, respaldado na política de drogas vigente no Brasil.

Interactions of anticancer drugs doxorubicin and idarubicin with lipid monolayers: New insight into the composition, structure and morphology

We quantify directly here for the first time the extents of interactions of two different anthracycline drugs with pure and mixed lipid monolayers with respect to the surface pressure and elucidate differences in the resulting interaction mechanisms. The work concerns interactions of doxorubicin (DOx) and idarubicin (IDA) with monolayers of the zwitterionic DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and negatively charged DMPS (1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (sodium salt)) as well as a 7:3 mixture of the two lipids. These drugs are used in current cancer treatments, while the lipid systems were chosen as phosphocholines are the major lipid component of healthy cell membranes, and phosphoserines are the major lipid component that is externalized into the outer leaflet of cancerous cell membranes. It is shown that DOx interacts with DMPS monolayers to a greater extent than with DMPC monolayers by lower limits of a factor of 5 at a surface pressure of 10 mN/m and a factor of 12 at 30 mN/m. With increasing surface pressure, the small amount of drug (~0.3 µmol/m2) bound to DMPC monolayers is excluded from the interface, yet its interaction with DMPS monolayers is enhanced until there is even more drug (~3.2 µmol/m2) than lipid (~2.6 µmol/m2) at the interface. Direct evidence is presented for all systems studied that upon surface area compression lipid is reproducibly expelled from the monolayer, which we infer to be in the form of drug-lipid aggregates, yet the nature of adsorption of material back to the monolayer upon expansion is system-dependent. At 30 mN/m, most relevant to human physiology, the interactions of DOx and IDA are starkly different. For DOx, there is a conformational change in the interfacial layer driven by aggregation, resulting in the formation of lateral domains that have extended layers of drug. For the more lipophilic IDA, there is penetration of the drug into the hydrophobic acyl chain region of the monolayer and no indication of lateral segregation. In addition to the Langmuir technique, these advances were made as a result of direct measurements of the interfacial composition, structure and morphology using two different implementations of neutron reflectometry and Brewster angle microscopy. The results provide new insight into key processes that determine the uptake of drugs such as limited drug penetration through cell membranes by passive diffusion as well as activation of drug removal mechanisms related to multidrug resistance.

Impact of Drug-Polymer Interaction in Amorphous Solid Dispersion Aiming for the Supersaturation of Poorly Soluble Drug in Biorelevant Medium.

The aim of this study was to investigate the influence of the production method and the polymeric carrier on the ability to generate and maintain the supersaturation of a poorly soluble drug in biorelevant medium. The amorphous solid dispersion of sulfamethoxazole, an antibacterial drug, was produced using two different polymers by spray-drying or hot melt extrusion methods. When Eudragit EPO was used, supersaturation was maintained up to 24h for both techniques at all drug-polymer proportions. However, when Soluplus was employed in hot melt extrusion, a smaller amount of drug was dissolved when compared to the amorphous drug. The proportion of 3:7 drug-Eudragit EPO (w/w) produced by spray-drying presented a higher amount of drug dissolved in supersaturation studies and it was able to maintain the physical stability under different storage conditions throughout the 90-day evaluation. Supersaturation generation and system stability were found to be related to more effective chemical interaction between the polymer and the drug provided by the production method, as revealed by the 1D ROESY NMR experiment. Investigation of drug-polymer interaction is critical in supersaturating drug delivery systems to avoid crystallization of the drug and to predict the effectiveness of the system. Chemical compounds studied in this article: Sulfamethoxazole (PubChem CID: 4539) and Methacrylate copolymer - Eudragit EPO (PubChem CID: 65358).

Legal sentences of adolescents for small-scale drug trafficking in Brazil: an analysis of judicial decisions

O objetivo do artigo é analisar os processos judiciais relativos ao ato infracional de tráfico de drogas, em Petrolina-PE (2011-2014), com base na revisão analítica das instituições e leis historicamente voltadas para a menoridade, segundo a Theory of Sentencing. Apreciouse o conteúdo social das variáveis legais e extralegais, analisando o efeito cumulativo dos determinantes das sentenças. As decisões judiciais mais encontradas foram extinção processual e absolvição. Medidas socioeducativas de advertência, liberdade e semiliberdade são mais recorrentes que a internação. No entanto, há disparidades das sentenças em casos análogos e imputação de penas análogas em casos díspares. Conclui-se que o sistema penal é produtor e reprodutor de desigualdades sociais e a punição é percebida e utilizada como técnica de controle e transformação de adolescentes pobres apreendidos com pequenas quantidades de drogas.

Dexamethasone pharmacokinetics characteristics via sub-tenon microfluidic system in uveitis rabbits

The aim of this study was to investigate the plasma and ocular dexamethasone (DEX) pharmacokinetics characteristics of the sub-tenon microfluidic system (SMS) delivery of dexamethasone sodium phosphate (DEXP) in experimental autoimmune uveitis (EAU) rabbits. The SMS showed sustained DEX release and large amount of drug loading capacity by a miniature pump which connected with a tube that implanted into the sub-Tenon's sac of the EAU rabbit. The DEX concentrations in the plasma and different ocular compartments (cornea, aqueous humor, retina/choroid, sclera and vitreous humor) were quantified by Shimadzu LC–MS 2010 system. The SMS increased total drug delivery of DEX in ocular tissues as compared with traditional combined medication (subconjunctival injection combined with intravenous injection) in EAU rabbit. Moreover, the minimal amount of DEX was found in the blood, indicated that only a small amount of drug could enter into the bloodstream and causing minimal systematic side effect. Overall, the study provided evidence that SMS meet the large amount of drug loading capacity, continuous release drugs and moderate drug level in the EAU ocular tissue and minimal drug level in the blood, which indicated that SMS could be a feasible option for ocular application in clinical trials and maybe can replace or even discard systemic medications for the management of acute ocular inflammation disease.

Multi-objective evolutionary design of antibiotic treatments.

Antibiotic resistance is one of the major challenges we face in modern times. Antibiotic use, especially their overuse, is the single most important driver of antibiotic resistance. Efforts have been made to reduce unnecessary drug prescriptions, but limited work is devoted to optimising dosage regimes when they are prescribed. The design of antibiotic treatments can be formulated as an optimisation problem where candidate solutions are encoded as vectors of dosages per day. The formulation naturally gives rise to competing objectives, as we want to maximise the treatment effectiveness while minimising the total drug use, the treatment duration and the concentration of antibiotic experienced by the patient. This article combines a recent mathematical model of bacterial growth including both susceptible and resistant bacteria, with a multi-objective evolutionary algorithm in order to automatically design successful antibiotic treatments. We consider alternative formulations combining relevant objectives and constraints. Our approach obtains shorter treatments, with improved success rates and smaller amounts of drug than the standard practice of administering daily fixed doses. These new treatments consistently involve a higher initial dose followed by lower tapered doses.

Often neglected: PLGA/PLA swelling orchestrates drug release: HME implants

Different types of poly(lactic-co-glycolic acid) (PLGA)- and poly(lactic acid) (PLA)-based implants for controlled dexamethasone release were prepared by hot melt extrusion (HME). The lactic acid:glycolic acid ratio was varied (50:50, 75:25, 100:0) as well as the drug loading (1–15%). Resomer RG 502H, RG 752H and R 202H (all with –COOH end groups) were studied. The implants were characterized before and after exposure to phosphate buffer pH 7.4 at 37 °C. Interestingly, in all cases polymer swelling seems to play an “orchestrating” role for drug release: At early time points, the amounts of water penetrating into the systems are limited (since the macromolecules are hydrophobic and highly entangled). Consequently, only small amounts of drug can dissolve and the dissolved drug molecules are not sufficiently mobile to diffuse out to a noteworthy extent (negligible dexamethasone release for up to 6 weeks). However, the water that is able to enter the implants at early time points cleaves the polyesters right from the beginning. Due to the newly generated –COOH end groups and decreased chain length, the macromolecules become more and more hydrophilic and less entangled. In addition, water-soluble polymer degradation products build up a steadily increasing osmotic pressure, attracting water into the system. Once a critical polymer molecular weight threshold range (around 8 kDa) is reached, substantial implant swelling starts: The systems' volume increases up to 600–1700% and the water contents exceeds 80–90% (partially approaching 100%). Under these fundamentally altered conditions, significant drug amounts can dissolve and the dissolved drug molecules are sufficiently mobile to diffuse out of the implants: Drug release sets on. In brief, polymer swelling “orchestrates” the involved mass transport phenomena: It enables drug release after a certain lag time by fundamentally changing the conditions for drug dissolution and diffusion. Note that in other types of implants, additional mass transport phenomena might be involved, e.g. no burst release was observed from the investigated, initially non-porous implants.

Novel biocompatible poly(acrylamide)-grafted-dextran hydrogels: Synthesis, characterization and biomedical applications

An electro-responsive PAAm-g-Dxt copolymer was synthesized and characterized by 1HNMR & FTIR spectroscopy, neutralization equivalent, elemental and thermogravimetric analysis to ascertain the grafting reaction. Further, we developed an electro-responsive transdermal drug delivery system (ETDS) utilizing PAAm-g-Dxt copolymer for rivastigmine tartarate delivery through skin. The ETDS were developed using drug-loaded PAAm-g-Dxt hydrogel as the reservoir, and cross-linked dextran-poly(vinyl alcohol) blend films as rate controlling membranes (RCM). In the absence of electrical stimuli, a small amount of drug was permeated from the ETDS, while in the presence of electrical stimuli, the drug permeability was increased. On application of electric stimulus, the flux was increased by 1.6 fold; drug permeability was enhanced when the strength of applied electric current was raised to 8 mA from 2 mA. The drug permeability characteristics studied under “on–off” stimuli suggested that there was faster drug permeation when electrical stimuli was ‘on’ and it decreased when electrical stimuli was ‘off.’ The histopathology study confirmed the altered skin structural integrity after application of electrical stimuli. Hence, the PAAm-g-Dxt based ETDS are useful for transdermal drug delivery triggered by an electric stimulus to deliver on-demand release of drug into systemic circulation.

Electro-responsive polyacrylamide-grafted-gum ghatti copolymer for transdermal drug delivery application

An application of polyacrylamide-grafted-gum ghatti (PAAm-g-GGH) copolymer for transdermal delivery of an anti-psychotic drug, quetiapine fumerate triggered by electric stimulus was explored. The electro-responsive PAAm-g-GGH was prepared by free radical polymerization underneath nitrogen atmosphere subsequent to alkaline hydrolysis. The PAAm-g-GGH was used as drug reservoir gel and crosslinked films of GGH and PVA as rate controlling membranes (RCM). The reservoir gels were uniform and translucent; pH of gels was 6.56–7.06, which is in the pH range of skin and drug content was from 89.57% to 94.51%. The thickness of RCMs was 163–227 μ; thickness was increased with increased glutaraldehyde concentration and all the RCMs were permeable to water vapors. When electric stimulus was absent, a small amount of drug was permeated from the formulations, while drug conveyance was enhanced in the existence of stimulus. Drug permeation was increased with increase in electric stimulus from 2 to 8 mA. Over two fold increase in flux was observed after application of electric stimulus. Under “on–off” electric stimulus, faster drug permeation was seen under ‘on’ condition and permeation was decreased when stimulus was ‘off.’ Histopathology study confirmed reversible alteration of skin structure under electric stimulus.

Encapsulation of ciprofloxacin within modified xanthan gum- chitosan based hydrogel for drug delivery

The aim of the present work was to investigate the preparation of polyelectrolyte hydrogel as potential drug carrier for antibacterial Ciprofloxacin drug (CFX), intended for controlled release formulation. Hydrogel of N-trimehtyl chitosan (TMC)/sodium carboxymethyl xanthan gum (CMXG) was prepared and ciprofloxacin was employed as a model drug to investigate the loading and release performance of the prepared hydrogel. FTIR, DSC, TGA and SEM analysis were used to characterize the TMC/CMXG hydrogel and its CFX loaded hydrogel. The results showed that the ciprofloxacin was successfully incorporated and released from the prepared hydrogel without the loss of structural integrity or the change in its functionality. The encapsulation efficiency of CFX within the prepared hydrogel was found to be increased with increasing the concentration of drug reaching about 93.8 ± 2.1% with concentration of CFX 250 µg/ml. It was shown also that the drug is entrapped within the gel without significant interaction as confirmed from FTIR spectra and DSC analysis. In vitro release study in phosphate buffer saline (PBS), indicated the steady rise in cumulative drug release with the highest release amount, reaching about 96.1 ± 1.8% up to 150 min, whereby the gel with high drug loading efficiency (3.52 ± 0.07%) displayed faster and higher release rate than that of gel containing a smaller amount of drug (0.44 ± 0.01%). The release kinetics of loaded drug followed zero-order kinetics. CFX drug loaded hydrogel showed high activity against the gram positive and gram negative bacterial strains due to the successful released of CFX from the CFX loaded hydrogel into the tested bacterial strains with the highest diameter of inhibition zone against Escherichia coli (67.0 ± 1.0) as compared to reference antibiotic, Gentamicin (28 ± 0.5). Cytotoxicity of the prepared hydrogel was examined in vitro using lung human normal cell lines and showed the highest cell viability (97 ± 0.5%) at concentration up to 50 µg/ml. Consequently, TMC/CMXG hydrogel can be proposed as new controlled release drug delivery system.

Formulation and Evaluation of Spray Dried Microspheres of Controlled Release Ramipril

The present study sought to develop and evaluate spray-dried microspheres of chitosan and xanthan gum for controlled release of ramipril, a widely used antihypertensive drug. The prepared microspheres were characterized by particle size analysis, scanning electron microscopic studies, differential scanning calorimetric analysis, Fourier transform infrared spectroscopy analysis, X-ray diffraction studies, drug entrapment efficiency, and in-vitro drug release study. The prepared microspheres were spherical in shape and freely flowing. The size of the microspheres was in the range of 25.7 to 47.4 µm and the drug entrapment efficiency was in the range of 74.68% to 90.44%. TheDSC analysis and X-ray diffraction studies indicated that the drug was uniformly dispersed in amorphous state in the microspheres. The in-vitro drug release indicated that the spray-dried microspheres prepared with chitosan alone were not suitable for controlled released delivery of drug as maximum amount of drug was released within 5 hrs. Whereas microspheres prepared by xanthan gum released small amount of drug within 5 hrs and more amount of drug was controlled released that fit the therapeutic needs. Drug release mechanism followed non-Fickian transport. These suggest the formulation potential of chitosan and xanthan gum for spray-dried microspheres for controlled release of ramipril

Design and Near-Infrared Actuation of a Gold Nanorod⁻Polymer Microelectromechanical Device for On-Demand Drug Delivery.

Polymeric drug delivery systems usually deliver drugs by diffusion with an initial burst of release followed by a slower prolonged release phase. An optimal system would release exact doses of drugs using an on-demand external actuation system. The purpose of this study was to design and characterize a novel drug-delivery device that utilizes near infrared (NIR 800 nm) laser-actuated drug release. The device was constructed from biocompatible polymers comprising a reservoir of drug covered by an elastic perforated diaphragm composed of a bilayer of two polymers with different thermal expansion coefficients (ethylenevinylacetate (EVA) and polydimethylsiloxane (PDMS) containing gold nanoparticles). Upon illumination with a NIR laser, the gold nanoparticles rapidly heated the bilayer resulting in bending and a drug-pumping action through the perforated bilayer, following sequential laser-actuation cycles. Devices filled with the anti-proliferative drug docetaxel were seen to release only small amounts of drug by diffusion but to release large and reproducible amounts of drug over 20 s laser-actuation periods. Because NIR 800 nm is tissue-penetrating without heating tissue, suitable geometry drug-delivery devices might be implanted in the body to be actuated by an externally applied NIR laser to allow for on-demand exact drug dosing in vivo.

Analytical Control of Pediatric Chemotherapy Preparations with a UV-Raman Automaton: Results After 18 Months of Implementation and Development of A Suitable Method for Low Volume Preparations

AbstractBackgroundIn France, control of chemotherapy preparations is highly recommended. Analytical control is a method of choice for identifying and quantifying drugs. Pediatric preparations, which often contain small quantities of drugs and are made in low final volumes were until then not analytically controlled. After the development and validation of a new sampling and assaying method for low volume chemotherapy preparations with an UV/Raman automaton (QCPrep +), the quality control results of the preparations intended for the patients were analyzed over a period of eighteen monthsMethodsThe results were studied by type of preparation (low and high volume), per molecule, manipulator, and conformity rates dispersion.ResultsOver the period, 7,548 controls were carried out, representing 87.7% of our production. 75.5% of these controls concerned low-volume preparations (<50mL). The overall conformity rate was 94.4%. The lowest conformity rates were found for vinca alkaloids, methotrexate and some rarely manipulated drugs (cisplatin, decitabine, epirubicin). The study of the results dispersion showed non-conformities increasing with low concentrations, specific to pediatrics. These results show the limits of analytical control for pediatric preparations. The low analytical sensitivity encountered for certain concentrations and drugs requires a complementary quality control tool, like camera or video. However this new analytical method allows us to improve the safety of the injectable chemotherapy circuit.ConclusionYoung patients can benefit from the same level of safety and quality as adult patients. Some critical points could be highlighted: the homogenization of the preparations, the analytical sensitivity of some drugs and human factors. This data allow us to focus our work on staff training, improving our calibration ranges and on the development of complementary control tools.