Nanocrystals- A substantial platform for drug delivery applications.

Poor solubility of a drug is one of the major concerns in drug delivery. Many strategies have been employed for solving this problem, but there are still some deficiencies with current strategies, such as low drug loading, high toxicity, poor stability, potential drug loss during storage and complex manufacturing method. By formulating nanocrystals, problems associated with the delivery of drugs with low water or lipid solubility can be addressed. Unlike polymeric nanoparticles and lipidic nanoparticles, they are not a reservoir or matrix system. Nanocrystals are colloidal suspensions of nanosized particles stabilized by polymeric or electrostatic stabilization. They can be prepared by Top-down or Bottom-up approaches. Some of the methods for the preparation of nanocrystals are nanoprecipitation, media milling, high-pressure homogenization, emulsions and microemulsions as templates, supercritical fluid technology and co-grinding. They can be used for oral, intravenous, ocular, inhalation, intramuscular drug delivery and drug targeting.

Critical Drug Loss Induced by Silicone and Polyurethane Implantable Catheters in a Simulated Infusion Setup with Three Model Drugs

Silicone and polyurethane are biocompatible materials used for the manufacture of implantable catheters, but are known to induce drug loss by sorption, causing potentially important clinical consequences. Despite this, their impact on the drugs infused through them is rarely studied, or they are studied individually and not part of a complete infusion setup. The aim of this work was to experimentally investigate the drug loss that these devices can cause, on their own and within a complete infusion setup. Paracetamol, diazepam, and insulin were chosen as models to assess drug sorption. Four commonly used silicone and polyurethane catheters were studied independently and as part of two different setups composed of a syringe, an extension set, and silicone or polyurethane implantable catheter. Simulated infusion through the catheter alone or through the complete setup were tested, at flowrates of 1 mL/h and 10 mL/h. Drug concentrations were monitored by liquid chromatography, and the silicone and polyurethane materials were characterized by ATR-IR spectroscopy and Zeta surface potential measurements. The losses observed with the complete setups followed the same trend as the losses induced individually by the most sorptive device of the setup. With the complete setups, no loss of paracetamol was observed, but diazepam and insulin maximum losses were respectively of 96.4 ± 0.9% and 54.0 ± 5.6%, when using a polyurethane catheter. Overall, catheters were shown to be the cause of some extremely high drug losses that could not be countered by optimizing the extension set in the setup.

A Multilayer Functionalized Drug-Eluting Balloon for Treatment of Coronary Artery Disease

Drug-eluting balloons (DEBs) have been mostly exploited as an interventional remedy for treating atherosclerosis instead of cardiovascular stents. However, the therapeutic efficacy of DEB is limited due to their low drug delivery capability to the disease site. The aim of our study was to load drugs onto a balloon catheter with preventing drug loss during transition time and maximizing drug transfer from the surface of DEBs to the cardiovascular wall. For this, a multilayer-coated balloon catheter, composed of PVP/Drug-loaded liposome/PVP, was suggested. The hydrophilic property of 1st layer, PVP, helps to separate drug layer in hydrophilic blood vessel, and the 2nd layer with Everolimus (EVL)-loaded liposome facilitates drug encapsulation and sustained release to the targeted lesions during inflation time. Additionally, a 3rd layer with PVP can protect the inner layer during transition time for preventing drug loss. The deionized water containing 20% ethanol was utilized to hydrate EVL-loaded liposome for efficient coating processes. The coating materials showed negligible toxicity in the cells and did not induce pro-inflammatory cytokine in human coronary artery smooth muscle cells (HCASMCs), even in case of inflammation induction through LPS. The results of hemocompatibility for coating materials exhibited that protein adsorption and platelet adhesion somewhat decreased with multilayer-coated materials as compared to bare Nylon tubes. The ex vivo experiments to confirm the feasibility of further applications of multilayer-coated strategy as a DEB system demonstrated efficient drug transfer of approximately 65% in the presence of the 1st layer, to the tissue in 60 s after treatment. Taken together, a functional DEB platform with such a multilayer coating approach would be widely utilized for percutaneous coronary intervention (PCI).

A Safe Way to Administer Drugs Through a Nutrition Tube—The Simple Suspension Method

The simple suspension method (SSM), developed by Kurata in 1997, is a way to suspend tablets and capsules in warm water for decay and suspension prior to their administration. This method is safe and has various advantages such as the avoidance of tube clogging and the loss of the drug. This study aimed to investigate whether a higher percentage of commonly used drugs could pass through nutrition tubes effectively using SSM, relative to that using the conventional crushing method. A tablet or capsule was inserted into a 20 mL syringe with warm water (at 55 °C). After 10 min, it was shaken in the syringe. The suspension liquid was injected into tubes of the following sizes: 8 Fr, 10 Fr, 12 Fr, 14 Fr, 16 Fr, and 18 Fr. A total of 3686 tablets and 432 capsules that are frequently used in Japan were tested. Using SSM, 3377 (91.6%) tablets and 359 (83.1%) capsules disintegrated within 10 min and passed through the tube without clogging it in the tube passage test. With the conventional crushing method, 2117 tablets (57.4%) and 272 capsules (63.0%) could be crushed. SSM reduced the risk of tube clogging and drug loss with more drugs than that with the conventional crushing method. The number of drugs indicated for administration by SSM is greater than that indicated by the conventional crushing method. Further studies are needed to consider its utility compared to conventional methods for dysphagia patients in clinical settings.

Potential remote drug delivery failures due to temperature-dependent viscosity and drug-loss of aqueous and emulsion-based fluids

The ability to inject wild animals from a distance using remote drug delivery systems (RDDS) is one of the most effective and humane practices in wildlife management. Several factors affect the successful administration of drugs using RDDS. For example, temperature-dependent viscosity change in aqueous (Newtonian) or water-in-oil emulsion (non-Newtonian) fluids, commonly used in tranquilizer and adjuvant-based vaccines, respectively, can potentially result in drug delivery failure. To better understand impacts due to viscosity changes, we investigated the fluid dynamics and ballistics involved in remote drug delivery. Our research was divided into two phases: we investigated the viscosimetric physics in the first phase to determine the fluid behavior under different temperature settings, simulating recommended storage temperature (7ºC), plus an ambient temperature (20ºC). In the second phase of our study, we assessed the drug delivery efficiency by specialized darts, using a precision CO2 projector and a blowgun. Efficiency assessment was done by comparing the original drug volume with the actual volume injected after firing the dart into a fresh pork hide mounted on a ballistic gel. Before testing, we configured the required minimum impact velocity for our parameters and intramuscular injection (determined as ˃ 40 m/sec). All executed dart-deployments performed satisfactorily, despite initial concerns of potential incomplete drug delivery, however, noteworthy drug loss was observed (˃10%) associated with drug residues in syringe/dart dead space and within the transfer needle. This could potentially result in inaccurate dosing depending on the drug used. Furthermore, the use of a blowgun for remote drug delivery (>3m) is discouraged, especially when using specialized darts, as the required minimum dart velocity for adequate penetration is difficult to reach, in addition to a loss of precision during targeting.

STUDY OF ISOTONICITY AND OCULAR IRRITATION OF CHLORAMPHENICOL IN SITU GEL

Objective: The objective of this study was to find out the isotonicity of chloramphenicol ophthalmic in situ gel and to know the irritating effect of its in the eyes of test animals, so it can be to maximize absorption of the drug in the eye, minimize drug loss before corneal penetration and safe to used. Methods: This study were started by making four aseptic formulations of in situ gel preparations with a comparison of the baseline concentrations of different Poloxamer 407 and HPMC, F1 (5: 0.45), F2 (10: 0.45), F3 (5: 1) and F4 (10: 1). Four aseptic of in situ gel preparations, followed by a qualitative isotonicity test using blood cells to see the comparison between control and test preparations, and ocular irritation test using the draize test method to determine the presence or absence of the irritation. Results: The results obtained from the isotonicity test showed that the four preparations have normal blood cells that similar with isotonic control solution; therefore, it can be said that the preparations have been made isotonic. The results of the ocular irritation test using the draize test method showed for each category, such as cornea, iris, conjunctiva and edema were zero. A zero value on the cornea indicates no ulceration or opacity, and the iris, conjunctiva and edema were normal. Conclusion: Chloramphenicol in situ gel are isotonic and do not cause irritation to the rabbit's eyes, so they are safe to use and the formulation can be used for further research until the final goal is obtained.

Formulation and Stability of Ataluren Eye Drop Oily Solution for Aniridia

Congenital aniridia is a rare and severe panocular disease characterized by a complete or partial iris defect clinically detectable at birth. The most common form of aniridia occurring in around 90% of cases is caused by PAX6 haploinsufficiency. The phenotype includes ptosis, nystagmus, corneal limbal insufficiency, glaucoma, cataract, optic nerve, and foveal hypoplasia. Ataluren eye drops aim to restore ocular surface PAX6 haploinsufficiency in aniridia-related keratopathy (ARK). However, there are currently no available forms of the ophthalmic solution. The objective of this study was to assess the physicochemical and microbiological stability of ataluren 1% eye drop in preservative-free low-density polyethylene (LDPE) bottle with an innovative insert that maintains sterility after opening. Because ataluren is a strongly lipophilic compound, the formulation is complex and involves a strategy based on co-solvents in an aqueous phase or an oily formulation capable of totally dissolving the active ingredient. The visual aspect, ataluren quantification by a stability-indicating chromatographic method, and microbiological sterility were analyzed. The oily formulation in castor oil and DMSO (10%) better protects ataluren hydrolysis and oxidative degradation and permits its complete solubilization. Throughout the 60 days period, the oily solution in the LDPE bottle remained clear without any precipitation or color modification, and no drug loss and no microbial development were detected. The demonstrated physical and microbiological stability of ataluren 1% eye drop formulation at 22–25 °C might facilitate clinical research in aniridia.

Systematic evaluation of particle loss during handling in the percutaneous transluminal angioplasty for eight different drug-coated balloons

Paclitaxel drug coated balloons (DCBs) should provide optimal drug transfer exclusively to the target tissue. The aim of this study was to evaluate the particle loss by handling during angioplasty. A robotic arm was developed for systematic and reproducible drug abrasion experiments. The contact force on eight different commercially available DCB types was gradually increased, and high-resolution microscopic images of the deflated and inflated balloons were recorded. Three types of DCBs were classified: no abrasion of the drug in both statuses (deflated and inflated), significant abrasion only in the inflated status, and significant abrasion in both statuses. Quantitative measurements via image processing confirmed the qualitative classification and showed changes of the drug area between 2.25 and 45.73% (13.28 ± 14.29%) in the deflated status, and between 1.66 and 40.41% (21.43 ± 16.48%) in the inflated status. The structures and compositions of the DCBs are different, some are significantly more susceptible to drug loss. Particle loss by handling during angioplasty leads to different paclitaxel doses in the target regions for same DCB types. Susceptibility to involuntary drug loss may cause side effects, such as varying effective paclitaxel doses, which may explain variations in studies regarding the therapeutic outcome.

Understanding IV antimicrobial drug losses: the importance of flushing infusion administration sets

Background IV drugs are commonly prescribed for inpatient treatment. Where administered as infusions, drug dose loss is incurred if the infusion line is not flushed. Underdosing of IV antimicrobials is of particular concern as reduced treatment efficacy increases the risk of patient deterioration (including sepsis) and development of antimicrobial resistance. Objectives To quantify drug loss, raise awareness and provide recommendations to address this patient safety risk effectively. Methods Percentage drug loss of 39 IV antimicrobials was calculated for a theoretical patient case scenario, using residual volumes for IV infusion lines utilized within this acute healthcare setting. An adult male patient (70 kg) with good renal function was assumed for drug dosing. Infusion volumes and doses are based on a widely used IV administration guide. Results Data revealed the scope and extent of antimicrobial drug losses where infusion lines were not flushed as ranging from 2% to 33%. More than 10% of the drug would be lost for 26 of the 39 antimicrobials assessed, with five of these yielding over 20% loss. Conclusions The authors suggest that unintentional antimicrobial underdosing is going unnoticed in clinical practice. Where IV infusion is necessary, flushing of the infusion line to ensure total dose administration is strongly recommended. Risks associated with flushing lines (fluid overloading, bolus dosing, etc.) can be managed with simple measures. The authors call for a national body-led approach to effectively influence healthcare organizations in review of IV administration protocols, ensuring patient safety and care in the NHS.