Drug Delivery Based on Micro Electro-Mechanical Systems: A Review

The aim of controlled drug delivery is to manage the time and site of drug release according to the patients’ need.In this paper, Micro Electro-Mechanical Systems (MEMS) technology is described.This technology employs microelectronics and microprocessor circuits in order to reach individualized, targeted and controlled drug release and would construct the future drug delivery systems. Introduction: Controlled drug delivery systems are the state of the art in drug delivery technology with the goal of controlling the drug release at right time and site to satisfy the patient’s pathophysiological requirements. In spite of great improvements in this field, it still remains an open research area.MEMS employs sophisticated systems in a small scale. In last few decades, this technology has increasingly attracted the researchers’ attention due to its successful miniaturization of complicated drug delivery systems to address unmet dosing requirements more precisely.MEMS drug delivery systems are fabricated using the microelectronics and microprocessor circuits of highly-advanced technology. This provides the opportunity to implement several drug reservoirs and billions of electronic devices in few millimeters. Methods and Results:In this study, MEMS technology is introduced along with describing the fabrication process. Two main categories of MEMS devices including internal and transdermal devices and their applications in drug delivery systems are presented. Various actuators applied in these devices are described, including electrical, electrochemical, electromechanical, and electrothermal types. Finally, emerging technologies and prospects are briefly reviewed. Conclusions: MEMS techniques can be easily combined with microprocessors and sensors to implement an intelligent system which can determine the proper drug dosage and release time according to the signals received by biosensors. When placed inside the body, biocompatibility and biofouling issues should be well-considered, since the device will remain in the patient’s body for a long time. Therefore, MEMS technology seems to be the future aspect of targeted drug delivery systems

Enhancing Solubility and Dissolution of Celecoxib by Nanocrystals

Introduction: Celecoxib is a weakly acidic drug and has low aqueous solubility (3–7 μg/ml). Low solubility of drugs in water results in poor bioavailability because the solubility of a drug is an important factor in determining its absorption rate. According to the Noyes–Whitney equation, the saturation solubility and dissolution rate of poorly water soluble drugs can be enhanced by reducing the particle size, which increases the total surface area. Nanocrystals possess outstanding features enabling to overcome the solubility problems of poorly soluble drugs. The objective of this study was to investigate the dissolution behavior improving effects of differently sized nanocrystals of a poorly soluble model drug, Celecoxib. Methods and Results: Nanocrystals were prepared by antisolvent precipitation followed by high pressure homogenization (HPH) technique in the presence of varying percentage of SLS as a stabilizer (0.2 or 0.4%) and rate of homogenization (26500 or 12500 rpm). The obtained nanoparticles were analyzed in terms of particle size distribution, polydispersity index, saturation solubility, thermal behavior (DSC) and dissolution behavior. The particle size of nanosuspensions was between 140 and 532 nm with poly dispersibility index less than 0.5. That minimum of particle size relate to formulation which contained 0.4% stabilizer with rate of 26500 rpm. This formulation also revealed the highest saturation solubility (18.1 µg/ml) and dissolution efficiency compared to pure Celecoxib. The DSC results indicated the absence of any interactions between drug and stabilizer. These studies showed a decrease in crystalinity of Celecoxib. Conclusions: All microcrystals significantly (P<0.05) increased Celecoxib aqueous solubility and dissolution rate compared to plain drug. This result seemed to be due the significant particle size reduction and decreased drug crystallinity. Significant influence of increasing in rate of homogenizer on size reduction was observed.  As well as, high stabilizer concentration and rate of homogenizer had Significant influence on saturated solubility of Celecoxib compared to pure drug (P<0.05). DSC study showed that there is no change in the crystal structure of Celecoxib during the process and showed that nanocrystals exhibited decreased crystallinity.          &nbsp

Formulation and evaluation of orally disintegrating tablet of ondansetron using natural superdisintegrant

Introduction: Difficulty in swallowing is common among all age groups, especially elderly and pediatrics. Orally disintegrating tablets may constitute an innovative dosage form that overcome the problem of swallowing and provide a quick onset of action. This study was aimed to formulate and evaluate an orally disintegrating tablet (ODT) containing ondansetron while using semi-synthetic and natural superdisintegrants. Methods: Orodispersible tablets were prepared by direct compression using natural superdisintegrant (Karaya gum) and semi-synthetic superdisintegrant (croscarmellose). The prepared tablets were evaluated for hardness, friability, thickness, drug content uniformity, water absorption and wetting time. A 32 factorial design was used to investigate the effect of independent variables (amount of croscarmellose and Karaya gum) on dependent variables (disintegration time, friability and Q5 cumulative amount of drug release after 5 minutes). A counter plot was also presented to graphically represent the effect of independent variable on the disintegration time, friability and Q5. The check point batch was also prepared to prove the validity of the evolved mathematical model. The systematic formulation approach helped in understanding the effect of formulation processing variable. Results: According to the results of optimized batches, the best concentrations of superdisintegrant were as follows: 7.88 mg Karaya gum and 7.78 mg croscarmellose gave rapid disintegration in 31 seconds which showed 99% drug release within 5 minutes. Conclusion: Karaya gum, a natural superdisintegrant, gives a rapid disintegration and high release when used with synthetic superdisintegrant in formulation of ODT.</p

Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model

The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the brain for a prolonged period. The objective of this study was delivery of valproic acid (VPA) to the brain by intranasal route. For this purpose, nanostructured lipid carriers (NLCs) were prepared by solvent diffusion method followed by ultrasonication and characterized for size, zeta potential, drug-loading percentage, and release. Six groups of rats each containing six animals received drug-loaded NLCs intraperitoneally (IP) or intranasally. Brain responses were then examined by using maximal electroshock (MES). The hind limb tonic extension:flexion inhibition ratio was measured at 15-, 30-, 60-, 90-, and 120-minute intervals. The drug concentration was also measured in plasma and brain at the most protective point using gas chromatography method. The particle size of NLCs was 154 ± 16 nm with drug-loading percentage of 47% ± 0.8% and drug release of 75% ± 1.9% after 21 days. In vivo results showed that there was a significant difference between protective effects of NLCs of VPA and control group 15, 30, 60, and 90 minutes after treatment via intranasal route (P < 0.05). Similar protective effect was observed in rats treated with NLCs of VPA in intranasal route and positive control in IP route (P > 0.05). Results of drug determination in brain and plasma showed that brain:plasma concentration ratio was much higher after intranasal administration of NLCs of VPA than the positive control group (IP route). In conclusion, intranasal administration of NLCs of VPA provided a better protection against MES seizure

Formulation and evaluation of orally disintegrating tablet of Rizatriptan using natural superdisintegrant

Introduction: Rizatriptan benzoate is a potent and selective 5-HT1B/1D receptor agonist and is effective for the treatment of acute migraine. Difficulty in swallowing is common among all age groups, especially elderly and pediatrics. Orally disintegrating tablets may constitute an innovative dosage form that overcome the problem of swallowing and provides a quick onset of action. This study was aimed to formulate and evaluate an Orally Disintegrating Tablet (ODT) containing Rizatriptan while using semi-synthetic and natural superdisintegrants. Methods: Orodispersible tablets were prepared by direct compression using natural superdisntegrant (Plantago ovata mucilage) and semi-synthetic superdisntegrant (crospovidone). The prepared tablets were evaluated for hardness, friability, thickness, drug content uniformity, water absorption and wetting time. A 32 factorial design was used to investigate the effect of independent variables (amount of crospovidone and Plantago ovata mucilage) on dependent variables disintegration time, wetting time and Q5 (cumulative amount of drug release after 5 minutes). A counter plot was also presented to graphically represent the effect of independent variable on the disintegration time, wetting time and Q5. The check point batch was also prepared to prove the validity of the evolved mathematical model. The systematic formulation approach helped in understanding the effect of formulation processing variable. Results: According to the results of optimized batches, the best concentration of superdisintegrant were as follows: 9.4 mg Psyllium mucilage and 8.32 mg crospovidone gave rapid disintegration in 35sec and showed 99% drug release within 5 minutes. Conclusion: Plantago ovata mucilage, a natural superdisintegrant, gives a rapid disintegration and high release when used with synthetic superdisntegrant in formulation of orally disintegrating tablet of Rizatriptan.</p

Formulation of LDL Targeted Nanostructured Lipid Carriers Loaded with Paclitaxel: A Detailed Study of Preparation, Freeze Drying Condition, and In Vitro

In the present study, cholesterol nanostructured lipid carriers with various oleic acid content loaded with paclitaxel (PTX) were prepared by solvent emulsification-diffusion method using a Taguchi design. Size, zeta potential, entrapment efficiency, drug loading, and release percent of NLCs were measured. The results indicated that the most effective factors on the size were oleic acid content and surfactant percent. Zeta potential was more affected by the drug content. Drug to- lipid weight ratio was the most effective factor on entrapment efficiency and drug release from NLC. In the present work, the effect of lyophilization on the particle size and release properties of NLCs was also evaluated. The results revealed no differences between the characteristics of NLCs before and after freeze drying by using 25% w/w sorbitol as cryoprotectant. Cytotoxicity studies indicate that PTX associated with the NLC is also effective in HT-29 cell lines and enters the cancer cells selectively through the LDL receptor endocytic pathway. The IC50 values of free PTX solubilized in Cremophor EL and NLC-born PTX after 72 h exposure were  ng/mL and  ng/mL, respectively

The Impact of the COVID-19 Pandemic on Nursing Simulation Use and the Influence of Simulation Use on Future Admissions

Nursing simulations have been used for over 100 years to better prepare nursing students and equip them with the medical and social skills necessary to provide high quality patient care. The use of simulation in nursing programs has helped students better their clinical skills, increase their confidence with patients, and practice with rare and difficult medical and social scenarios. With states approving up to 50% replacement of clinical hours with simulation hours, many schools have taken this opportunity to provide their students with the technology. With the onset of the COVID pandemic, clinical placements were suspended, and nursing programs turned to virtual simulations. The California Board of Nursing (BON) increased their approval to 75% replacement of clinical hours (AB2288) and, based on the results of this study, the vast majority of California nursing programs increased their percent of simulation use by 100% on average. Simulation was used to replace a higher percent of clinical hours than ever before. This explanatory sequential mixed methods study included a survey, followed by an interview to understand how simulation use changed as a result of the COVID pandemic and explore ways in which simulation technology can impact nursing school admissions for the future. For the quantitative portion, surveys were sent to simulation leaders at 128 of the 149 nursing programs in California, and 43 completed the survey (a 34% response rate). The survey revealed that 90% of programs increased their simulation use overall during the pandemic, 92% of respondents stated that the increase was necessary to address a scarcity of clinical placements, and the percent of clinical hours replaced by simulation during the pandemic rose from an average of 16% to 40%. After the pandemic, 68% of respondents predicted that they would use more simulation than they did before the pandemic, which suggests that schools have increased their buy-in to the benefits of the technology. Lastly, 31% of respondents stated that they were able to increase admission offers in 2020 because of increased simulation use. From the survey data collected, I interviewed simulation leaders of 5 nursing programs at which simulation impacted enrollment in the past, currently or had a predicted impact on future enrollment. Interviews were conducted virtually and further confirmed that increasing simulation use for the replacement of clinical hours could allow the enrollment of more students. If each student requires fewer clinical placement hours because a higher percent of these hours can be replaced by simulation, then the available clinical placement hours can be spread across more students. However, all interview respondents stated the next biggest barrier of increasing enrollment, insufficient number of faculty, would stifle any hopes of enrolling more students. Program leaders reported highly positive perceptions of the effectiveness of simulation on student NCLEX scores as well as their clinical competence. Respondents noted that the top three motivators for increasing simulation use before the pandemic was to practice clinical skills, expose students to rare scenarios and assess students’ clinical skills. During the pandemic, the top three motivators shifted; an overwhelmingly high percent of respondents (92%) stated that the top reason for increasing simulation was to address the scarcity of clinical placements. Although most nursing programs have increased their simulation substantially, there are still programs that are nowhere near the maximum allowable usage. The Diffusion of Innovation theory categorizes schools that have not fully integrated the innovation as being in the implementation stage. Applying the theory and understanding the history and current state of simulation use may help more California programs diffuse the technology, meet the maximum allowable replacement of clinical hours, and use the clinical placements that have opened to increase student admissions

Preparation and Evaluation of Lipid-Based Liquid Crystalline Formulation of Fenofibrate

Background: Many drugs have poor water solubility and so the oral delivery of such drugs is usually associated with limitation of low bioavailability and lack of dose proportionality. Lipid-based liquid crystal (LC) systems are excellent potential formulations for increasing dissolution and bioavailability of drugs. The aim of the present study was to formulate lipid-based LC containing fenofibrate (FFB) as a hydrophobic drug. Materials and Methods: The studied variables included lipid and stabilizer concentrations and the type of stabilizer. The LC formation was identified by the polarized optical microscopic method. The effects of variables on formulation characteristics such as particle size, drug release, and rheological behavior were evaluated. Results: The results showed that the prepared formulations had the particle size between 42 and 503 nm. The drug release profiles showed that FFB had the continuous release from the formulations and the highest dissolution efficiency was seen in formulation prepared by 1.5% of glyceryl monostearate and 0.5% of Pluronic F127 as the stabilizer. The change of stabilizer type from colloidal silica to Pluronic F127 increased the drug release, significantly. Conclusions: In the most formulations of FFB LCs, the DE% was more than the pure drug, and therefore, it seems that the liquid crystalline formulations can be effective for enhancing drug release. Furthermore, drug release rate depended on the stabilizer type so that the presence of colloidal silica caused slower drug release compared to Pluronic F127

Formulation and evaluation of orally disintegrating tablet of ondansetron using natural superdisintegrant

Introduction: Difficulty in swallowing is common among all age groups, especially elderly and pediatrics. Orally disintegrating tablets may constitute an innovative dosage form that overcome the problem of swallowing and provide a quick onset of action. This study was aimed to formulate and evaluate an orally disintegrating tablet (ODT) containing ondansetron while using semi-synthetic and natural superdisintegrants. Methods: Orodispersible tablets were prepared by direct compression using natural superdisintegrant (Karaya gum) and semi-synthetic superdisintegrant (croscarmellose). The prepared tablets were evaluated for hardness, friability, thickness, drug content uniformity, water absorption and wetting time. A 32 factorial design was used to investigate the effect of independent variables (amount of croscarmellose and Karaya gum) on dependent variables (disintegration time, friability and Q5 [cumulative amount of drug release after 5 minutes]). A counter plot was also presented to graphically represent the effect of independent variable on the disintegration time, friability and Q5. The check point batch was also prepared to prove the validity of the evolved mathematical model. The systematic formulation approach helped in understanding the effect of formulation processing variable. Results: According to the results of optimized batches, the best concentrations of superdisintegrant were as follows: 7.88 mg Karaya gum and 7.78 mg croscarmellose gave rapid disintegration in 31 seconds which showed 99% drug release within 5 minutes. Conclusion: Karaya gum, a natural superdisintegrant, gives a rapid disintegration and high release when used with synthetic superdisintegrant in formulation of ODT