Influence of additives on swelling and mucoadhesion properties of glyceryl monooleate liquid crystals

Abstract Liquid crystalline systems of glyceryl monooleate/water are used as drug delivery systems due to their complex structure that controls drug diffusion. Mucoadhesive properties of glyceryl monooleate suggest it can be used for buccal delivery. Using additives is a strategy to modify physical and chemical properties of liquid crystalline systems and optimize their performance as a drug delivery system. However, the presence of additives can significantly alter properties such as phase behavior, swelling and mucoadhesion. Our aim is to investigate the influence of additives on swelling and mucoadhesion of glyceryl monooleate-based liquid crystals, intending them to be used as buccal drug delivery systems. The systems were characterized regarding their mesophases, swelling rate, and mucoadhesion. All the systems studied were able to absorb water and presented mucoadhesion, which is interesting for the development of buccal drug delivery systems. Additives induced phase transitions and affected the swelling performance, while mucoadhesive properties were poorly affected. Propylene glycol increased water uptake, while oleic acid induced the phase transition to the hexagonal phase and reduced the swelling rate. The association of oleic acid (5%) and propylene glycol (10%) resulted in a cubic phase system with strong mucoadhesive properties that can be a potential drug carrier for buccal delivery.

Profiling the physicochemical and solid state properties of edible Tetracarpidium conophorum oil and its admixtures for drug delivery

Abstract The study is aimed at investigating the functional physicochemical and solid state characteristics of food-grade Tetracarpidium conophorum (T. conophorum) oil for possible application in the pharmaceutical industry for drug delivery. The oil was obtained by cold hexane extraction and its physicochemical properties including viscosity, pH, peroxide, acid, and thiobarbituric acid values, nutrient content, and fatty acid profile were determined. Admixtures of the oil with Softisan®154, a hydrogenated solid lipid from palm oil, were prepared to obtain matrices which were evaluated by differential scanning calorimetry, fourier-transform infrared spectroscopy, and x-ray diffractometry. Data from the study showed that T. conophorum oil had Newtonian flow behaviour, acidic pH, insignificant presence of hyperperoxides and malondialdehyde, contains minerals including calcium, magnesium, zinc, copper, manganese, iron, selenium, and potassium, vitamins including niacin (B3), thiamine (B1), cyanocobalamine (B12), ascorbic acid (C), and tocopherol (E), and long-chain saturated and unsaturated fatty acids including n-hexadecanoic acid, 9(Z)-octadecenoic acid, and cis-13-octadecenoic acid. The lipid matrices had low crystallinity and enthalpy values with increased amorphicity, and showed no destructive intermolecular interaction or incompatibility between T. conophorum oil and Softisan® 154. In conclusion, the results have shown that, in addition to T. conophorum oil being useful as food, it will also be an important excipient for the development of novel, safe, and effective lipid-based drug delivery systems.

Progress in Research and Application of Drug-Device Combination Product / 中国医疗器械杂志

Drug-device combination product, which comprises at least a drug and a medical device, has been proved to effectively reduce the risk of complications accompanied with conventional medical devices implantation, and has a great clinical success especially in implantable therapeutics. Herein, we firstly elaborated the definitions and requirements of drug-device combination product in different countries, then summarized the market application and research development of typical drug-device combination products. Technical problems and the trend of future development had also been analyzed.

Development, in vitro biocompatibility, and antitumor efficacy of acetic acid-modified Cordyceps sinensis polysaccharide nanoparticle drug delivery system

Docetaxel-loaded acetic acid conjugated Cordyceps sinensis polysaccharide (DTX-AA-CSP) nanoparticles were prepared through dialysis and their release rates in vitro, particle sizes, zeta potentials, drug loading capacities, and encapsulation efficiencies were characterized for the synthesis of AA-modified CSPs from traditional Chinese medicine Cordyceps sinensis (Berk.) Sacc. Then, the AA-modified CSPs were characterized by 1H-NMR and FT-IR. Furthermore, the biocompatibility of the delivery carrier (AA-CSP nanoparticles) was assessed on human umbilical vein endothelial cells. In vitro antitumor activity studies on DTX-AA-CSP nanoparticles were conducted on the human liver (HepG2) and colon cancer cells (SW480). The DTX-AA-CSP nanoparticles were spherical and had an average size of 98.91±0.29 nm and zeta potential within the −19.75±1.13 mV. The encapsulation efficiency and loading capacity were 80.95%±0.43% and 8.09%±0.04%, respectively. In vitro, DTX from the DTX-AA-CSP nanoparticles exhibited a sustained release, and the anticancer activities of DTX-AA-CSP nanoparticles against SW480 and HepG2 were significantly higher than those of marketed docetaxel injection (Taxotere®) in nearly all the tested concentrations. The AA-CSP nanoparticles showed good biocompatibility. This study provided a promising biocompatible delivery system for carrying antitumor drugs for cancer therapy

A prototype single-port device for pressurized intraperitoneal aerosol chemotherapy. Technical feasibility and local drug distribution

Abstract Purpose: To evaluate the technical feasibility and homogeneity of drug distribution of pressurized intraperitoneal aerosol chemotherapy (PIPAC) based on a novel process of intraperitoneal drug application (multidirectional aerosolization). Methods: This was an in vivo experimental study in pigs. A single-port device was manufactured at the smallest diameter possible for multidirectional aerosolization of the chemotherapeutic drug under positive intraperitoneal pressure. Four domestic pigs were used in the study, one control animal that received multidirectional microjets of 9 mL/sec for 30 min and three animals that received multidirectional aerosolization (pig 02: 9 mL/sec for 30 min; pigs 03 and 04: 3 mL/sec for 15 min). Aerosolized silver nitrate solution was applied for anatomopathological evaluation of intraperitoneal drug distribution. Results: Injection time was able to maintain the pneumoperitoneum pressure below 20 mmHg. The rate of moderate silver nitrate staining was 45.4% for pig 01, 36.3% for pig 02, 36.3% for pig 03, and 72.7% for pig 04. Conclusions: Intra-abdominal drug distribution had a broad pattern, especially in animals exposed to the drug for 30 min. Our sample of only four animals was not large enough to demonstrate an association between aerosolization and a higher silver nitrate concentration in the stained abdominal regions.

The main potentialities of resveratrol for drug delivery systems

Resveratrol (RSV), a natural polyphenol found in grapes, was found to be effective in the prevention and therapy of several diseases, however, it does have unfavourable physicochemical properties. In this context, an increasing number of studies have aimed at developing novel therapeutic systems for its delivery to overcome these disadvantages. This review focuses on the mechanisms of action and therapeutic applications. Finally, it also describes some tested formulations for RSV administration, controlled release and targeting, developed with the purpose of increasing RSV bioavailability.

O resveratrol (RSV) é um polifenol natural encontrado nas uvas, que se mostrou eficaz na prevenção e terapia de várias doenças. No entanto, apresenta propriedades físico-químicas desfavoráveis. Neste contexto, um número cada vez maior de estudos visando ao desenvolvimento de novos sistemas terapêuticos para a sua liberação vem sendo desenvolvido no sentido de ultrapassar estas desvantagens. Esta revisão discorre sobre os mecanismos de ação e aplicações terapêuticas do RSV. Finalmente, são abordadas algumas formulações de liberação controlada e vetorizada, testadas para administração do RSV, desenvolvidas com a finalidade de aumentar a biodisponibilidade do RSV.

Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats

New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 microm, and the diameter of 89.93% of all microspheres ranged from 7.0 microm to 30.0 microm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t(1/2beta)) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to infinity (AUC(0-infinity)) was increased from 11.66 h.microg/g to 508.00 h.microg/g. The peak concentration (Cmax) in lung was increased from 5.95 microg/g to 93.36 microg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities.

Percepção da administração tópica ocular de drogas: aplicador facial x gotas / Topical drug administration perception with and without eye drop applicator

OBJETIVOS: Avaliar por meio de questionário, qual o grau de dificuldade para aplicação tópica de medicações oculares, com ou sem o auxílio do apoio facial. Observar qual método foi tecnicamente melhor utilizado para aplicação de drogas tópicas oculares. MÉTODOS: O estudo foi um ensaio clínico controlado e randomizado, realizado em 50 pacientes no decorrer de 2009 e 2010 na Unidade de Saúde da Família - Lapa. Foi utilizado um frasco de colírio Oftane® e o mesmo foi acoplado ao dispositivo de apoio facial. Cada participante aplicou em cada um dos olhos, a solução com ou sem o uso do dispositivo, sendo que a seleção foi feita através de um processo randomizado. Foi perguntado ao paciente questões pré-formuladas sobre a praticidade de ambos os métodos. RESULTADOS: Considerando o grau de dificuldade de administração tópica ocular: 12 por cento acharam difícil ou muito difícil a aplicação com o objeto de apoio facial e 22 por cento sem o apoio (p=0,0024). As dificuldades descritas pelos pacientes foram relatadas por 22 por cento dos pacientes para aplicação com o dispositivo de apoio facial e por 46 por cento para aplicação sem o mesmo. Já 34 por cento dos pacientes necessitaram de mais de uma instilação para aplicação do colírio sem o apoio, enquanto que 54 por cento dos pacientes precisaram de mais de uma aplicação para que a gota atingisse o olho com o auxílio do apoio facial (p= 0,04). Em 56 por cento dos pacientes houve toque da ponta do colírio com os tecidos oculares, quando o objeto de apoio facial não foi usado, porém quando ele foi utilizado, apenas 2 por cento dos pacientes observados tocaram os tecidos oculares (p=0,0001). CONCLUSÃO: É mais fácil a instilação de colírios com o auxílio do dispositivo de apoio facial. Este também dificulta o contato da ponta do frasco com os tecidos oculares, prevenindo a contaminação do frasco.

OBJECTIVE: Evaluate how difficult it is to apply ocular topical medications with and without an eye dropper facial applicator based on patient observation and answers to a questionnaire. METHODS: The study was a controlled and randomized clinical trial performed in 50 patients during the years of 2009 and 2010 in PSF - Lapa. Eye drops were applied with and without aid of an eye dropper facial applicator. Each individual tested applied randomly on one of their eyes an eye drop with or without the applicator. The patients had to answer questions about the practice concerning both forms of topical eye drug application. RESULTS: 12 percent informed that it was difficult or very difficult to instill eye drops and 22 percent to instill eye drops helped by an eye dropper facial applicator (0,0024). Problems described by patients were considered by 22 percent for eye drops with the applicator and by 46 percent for topical eye drop instillation without it. 34 percent of the patients needed more than one eye drop application to have eye drop contact , while 54 percent of the patients needed more than one application with the eye drop facial applicator in order to get drug eye contact (p= 0,04). In 56 percent of patients there were an eyedropper tip contact with ocular tissues, however there was only 2 percent of contact when the eye drop was instilled aided by the applicator (p=0,0001). CONCLUSION: It is easier to instill an eye drop with the help of an eye dropper applicator than without it. This dispositive also reduces the eyedropper tip contact with the ocular tissues.

Slow-release fluoride devices: a literature review

Although the prevalence of caries has decreased dramatically over the past decades, it has become a polarised disease, with most of subjects presenting low caries levels and few individuals accounting for most of the caries affected surfaces. Thus it become evident for the need of clinical approaches directed at these high-risk patients, in order to overcome problems related to compliance and low attendance at dental care centres. Slow-release fluoride devices were developed based on the inverse relationship existing between intra-oral fluoride levels and dental caries experience. The two main types of slow-release devices - copolymer membrane type and glass bead - are addressed in the present review. A substantial number of studies have demonstrated that these devices are effective in raising intra-oral F concentrations at levels able to reduce enamel solubility, resulting in a caries-protective effect. Studies in animals and humans demonstrated that the use of these devices was able to also protect the occlusal surfaces, not normally protected by conventional fluoride regimens. However, retention rates have been shown to be the main problem related to these devices and still requires further improvements. Although the results of these studies are very promising, further randomised clinical trials are needed in order to validate the use of these devices in clinical practice. The concept of continuously providing low levels of intra-oral fluoride has great potential for caries prevention in high caries-risk groups.

Transdermal permeation of trimetazidine from nerodilol-based HPMC gel drug reservoir system across rat epidermis

To study the in vitro transdermal permeation of trimetazidine from hydroxypropylmethyl cellulose [HPMC] gel drug reservoir system using nerodilol as a penetration enhancer. An HPMC gel containing selected concentrations of nerodilol [0, 2, 4 or 5% w/v] and 2.5% w/v of trimetazidine was prepared, and subjected to in vitro permeation studies across rat epidermis. The amount of trimetazidine permeated at different time intervals [1, 2, 4, 8, 12, 18 and 24 h] was estimated, and the data were analyzed to calculate various permeation parameters. There was an increase in the amount of trimetazidine [8,719.7 +/- 153.3 micro g/cm[2]] permeated across the rat epidermis up to 24 h [Q[24]] with an increase in nerodilol concentration [5% w/v] in HPMC gel drug reservoir. However, no significant difference [p > 0.05] was observed in the amount of drug permeated [Q[24]] with 5% w/v of nerodilol when compared to that obtained with 4% w/v of nerodilol [8,484.5 +/- 165.8 micro g/ cm[2]]. Nerodilol, at a concentration of 4% w/v enhanced the flux of trimetazidine across rat epidermis by about 1.96 times when compared to control. The HPMC gel drug reservoir containing 4% w/v of nerodilol showed optimal transdermal permeation of trimetazidine

Plastic bottles as spacers for a pressurized metered-dose inhaler: in vitro characteristics

Homemade spacer devices are commonly used by children with asthma to improve aerosol deposition from pressurized metered dose inhalers (pMDI); however, the efficacy and efficiency of these devices are not fully characterized. We determined the quality of fine particle fraction (< 4.7 microns) and ultrafine particle fraction (< 3.3 microns) of three bottles (from 280 ml to 500 ml) commonly used as spacers in Trinidad and Tobago and compared their performance to the commercially available valved holding chamber (OpT) and pMDI. These data were obtained in vitro using a cascade impactor. All 3 bottles and the OpT were similar (p > 0.05) in reducing the amount of albuterol emitted as large particles (> 4.7 microns) to less than 10 micrograms. The different sized bottles (from 280 ml to 500 ml) produced identical quantities of albuterol in the fine particle and ultrafine particle ranges (p > 0.05). All of the sample bottle spacers emitted a higher amount (p < 0.002) of fine and ultrafine particles than the OpT and pMDI alone. The OpT resulted in a significantly higher fraction of fine particles (p < 0.05) and a greater quantity of drug (p < 0.05) in the ultrafine range as compared to the MDI only. The sizes of particles obtained from the bottle spacers are those that have a high probability of reaching the lower airway; however, the clinical relevance of these findings remains to be determined.

Comparative efficiency of commercial and improvised spacer device in acute bronchial asthma.

OBJECTIVE: To compare the efficacy of a commercial spacer device versus an improvised spacer device in delivering aerosolized beta-2 agonist through metered dose inhaler in an acute exacerbation of bronchial asthma. DESIGN: Randomized controlled trial. SETTING: Urban tertiary care teaching hospital. METHODS: 60 children between 1 to 12 years of age with acute asthma were prospectively enrolled and randomized into two groups. Detailed history, clinical evaluation and appropriate laboratory investigations were recorded on a pretested proforma. One group received inhaled salbutamol using metered dose inhaler via commercial spacer device (Group 1), while the other received it via improvised spacer device (Group II). The response was sequentially assessed after 20, 40 and 60 minutes of institution of therapy. RESULTS:The two groups were comparable with respect to various parameters at presentation (p > 0.05). All the outcome parameters showed a significant improvement with time in both groups (p < 0.05). There was no statistical difference between the response in the two groups (p< 0.05). CONCLUSION: Metered dose inhaler with improvised spacer device is equivalent in efficacy and a more cost effective alternative to metered dose inhaler with commercial spacer for administration of beta-2 agonist in acute asthma.

Growth hormone therapy with a new delivery system.

Until recently the general regimen for treatment of growth hormone deficient (GHD) children consisted of 2 to 3 intramuscular (i.m.) injections per week using conventional syringes and vials. However, studies within the last 5-10 year have shown that by dividing the same total weekly dosage into daily subcutaneous (s.c.) injections it is possible to achieve a significantly increased growth rate. To make it more feasible for the patients and the parents to cope with this increased number of injections, an injection pen system (Nordiject) for administration of B-hGH has been developed. The Nordiject pen has been investigated both with respect to patient acceptance and bioavailability of the B-hGH (Norditropin) injected with the device. Twenty-seven children with growth retardation were included in a study. The patients had no problems with the handling of the pen and approximately 2/3 of them experienced less injection pain with the pen compared to the syringe. Those patients who had previously been using conventional syringes strongly preferred the pen, and all wished to continue using the device. Fourteen adult GHD patients were included in a randomized cross-over study for investigation of bioavailability. Two separate s.c. injections of 4 IU of B-hGH (Norditropin) each were administered in random order by means of either syringe (4IU/ml) or injection pen (Nordiject) (12 IU/ml). On the basis of this study it was concluded that the bioavailability of B-hGH, measured as AUC, Cmax, and tmax, is equal following injection with the pen to that of injection by syringe.