A COMPREHENSIVE REVIEW ON MICRONEEDLES - AN ARCHETYPE SWING IN TRANSDERMAL DRUG DELIVERY

Transdermal drug delivery is the non-invasive delivery of medications through the skin surface into the systemic circulation. The advantage of transdermal drug delivery system is that it is painless technique of administration of drugs. The advantage of transdermal drug delivery system is that it is painless technique of administration of drugs. Transdermal drug delivery system can improve the therapeutic efficacy and safety of the drugs because drug delivered through the skin at a predetermined and controlled rate. Due to the various biomedical benefits, it has attracted many researches. The barrier nature of stratumcorneum poses a danger to the drug delivery. By using microneedles, a pathway into the human body can be recognized which allow transportation of macromolecular drugs such as insulin or vaccine. These microneedles only penetrate outer layers of the skin, exterior sufficient not to reach the nerve receptors of the deeper skin. Thus the microneedles supplement is supposed painless and reduces the infection and injuries. Researches from the past few years showed that microneedles have emerged as a novel carrier and considered to be effective for safe and improved delivery of the different drugs. Microneedles development is created a new pathway in the drug delivery field. This review focus on new advances in transdermal drug delivery system using various carriers emphasizing mostly on the potential role of microneedles as transdermal system

DESIGNING AND QUALITY ASPECTS OF ASEPTIC PROCESS SIMULATION

Aseptic process simulation is a crucial validation technique carried out before a new product or aseptic process is introduced in the facility and also to prove on regular intervals that the existing manufacturing operations are carried out in a state of aseptic conditions. Aseptic process simulation involves conducting aseptic production using a sterile growth medium instead of actual drug solution and excipients. The processes involved in aseptic validation include the identification of process mechanisms, variables and control methods and that also include product, component, and sterilization of equipment, sanitary facilities, environmental checks and staff training on gowning procedure. This review addresses the nature of the study involved in aseptic process simulation, speed and number of runs, runtime, the atmospheric conditions, line speed, the media used, incubating and analyzing media-filled units, data interpretation, worst-case parameters, interventions, case study on interventions and the regulatory aspects concerned with the simulation

Formulation Design and Evaluation of Hydrogel-Based Metronidazole Bioadhesive Tablet for Vaginal Candidiasis: Hydrogel based tablet for vaginal candidiasis

Hydrogel-Based Metronidazole Bioadhesive Tablet (HMBT) was prepared as a novel vaginal delivery system to achieve Controlled release of drug from the tablet for vaginal candidiasis. The highly swollen hydrogel were prepared by dissolving chitosan in acetic acid solution containing drug, followed by neutralisation with sodium hydroxide and characterized by SEM, DSC and FT-IR and evaluated for % swelling. The drug loaded hydrogels were incorporated into tablet formulation by dry granulation method using bioadhesive polymers such as HPMC, sodium CMC and guar gum in different ratios. HMBT was tested for drug content, hardness, friability, weight variation, thickness, swelling studies, in vitro drug release, bioadhesive strength, in vivo studies and antifungal activity. The FT-IR and DSC spectra’s revealed that there was no chemical interaction between drug and polymers used. SEM revealed that particles of hydrogels appeared small and irregular shaped with large numbers of pores. F3 formulation shows good in vitro release profile with highest bioadhesive strength. From the in vivo study in rabbit it was found that the HMBT hold the tablet for more than 12 hours inside the vaginal tube. It may be concluded from present study that HMBT can be used as a novel delivery system for local therapy of vaginal candidiasis which can controlled the release of drug for prolong period of time

QBD-BASED DEVELOPMENT OF ORODISPERSIBLE FILMS OF ANTIPSYCHOTIC DRUGS

This review provides an overview of the application of the Quality by Design (QbD) approach in the formulation and evaluation of the orodispersible films (ODFs) of antipsychotic drugs. Quality by Design involves a well-defined approach with predefined objectives to develop the product or process based on quality risk management and sound science. It comprises the defining of Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQAs), risk assessment, design and development, and evaluation of formulation. The Orodispersible films are ultra-thin, elegant, and portable dosage forms that do not require water to be ingested. It can be used for individuals who require special needs, such as for treating psychosis, schizophrenia, mania, and dysphagia. Hence, it holds tremendous potential in terms of patient compliance, convenience, and pharmacotherapy. They are fabricated by different techniques, which include solvent casting, hot-melt extrusion, 3D printing, and others discussed here. They are evaluated for different attributes like mechanical strength, dissolution, disintegration, tensile strength, folding endurance, and others discussed here. It also provides the significance of stability, packaging, shapes, and patent-related concepts of orodispersible films

Formulation, Characterization, and Evaluation of Eudragit-Coated Saxagliptin Nanoparticles Using 3 Factorial Design Modules

Background and Introduction: Saxagliptin is a hypoglycemic drug that acts as a dipeptidyl peptidase-4 (DPP-4) inhibitor and is preferably used in the treatment of Type 2 Diabetes Mellitus (T2DM). It is safe and tolerable; however, the major disadvantage associated with it is its low bioavailability. Aim: The present research aimed to enhance the bioavailability of the drug by enteric coating with a polymer that controls the rate of drug delivery, and it was prepared as Solid Lipid Nanoparticles (SLNs). Methodology: In the current study, various SLN formulations were developed using a central composite design (CCD) module using Design Expert-11 software. A modified solvent injection technique was used to prepare Saxagliptin nanoparticles coated with Eudragit RS100. The CCD was used to determine the independent variables and their effect on dependent variables at varied levels. Evaluation studies such as particle size analysis, Zeta potential, polydispersity index (PDI), drug loading, entrapment efficiency, in-vitro drug release studies, and in vivo pharmacokinetic studies were performed for the optimized SLN formulation. The reversed-phase HPLC method was developed and validated for the estimation of the pharmacokinetic parameters of the pure drug and prepared SLNs. Results: The effect of independent variables (A1: amount of lipid, A2: amount of polymer, A3: surfactant concentration, and A4: homogenization speed) on dependent variables (R1: particle size, and R2: entrapment efficiency) was established in great detail. Observed responses of the prepared and optimized Saxagliptin SLN were close to the predicted values by the CCD. The prepared SLNs depicted particle sizes in the range of 212–442 nm. The particle size analysis results showed that an increase in the lipid concentration led to an increase in particle size. The developed bioanalytical method was noted to be very specific and robust. The method accuracy varied from 99.16% to 101.95% for intraday, and 96.08% to 103.12% for inter day operation at low (5 mcg/mL), moderate (10 mcg/mL), and higher (15 mcg/mL) drug concentrations. The observed Zeta potential values for the prepared SLNs were in the range of −41.09 ± 0.11 to 30.86 ± 0.63 mV suggesting quite good stability of the SLNs without any aggregation. Moreover, the polydispersity indices were in the range of 0.26 ± 0.051 to 0.45 ± 0.017, indicative of uniformity of sizes among the prepared SLNs. In vivo study outcomes proved that Saxagliptin oral bioavailability significantly enhanced in male Albino Wistar Rats via SLN formulation and Eudragit RS100 coating approach. Conclusions: The developed and optimized Saxagliptin SLNs revealed enhanced Saxagliptin bioavailability in comparison to the native drug. Thus, this formulation strategy can be of great importance and can be implied as a promising approach to enhance the Saxagliptin bioavailability for facilitated T2DM therapy

Sub-500 fs electronically nonadiabatic chemical dynamics of energetic molecules from the S-1 excited state: Ab initio multiple spawning study

Energetic materials store a large amount of chemical energy. Different ignition processes, including laser ignition and shock or compression wave, initiate the energy release process by first promoting energetic molecules to the electronically excited states. This is why a full understanding of initial steps of the chemical dynamics of energetic molecules from the excited electronic states is highly desirable. In general, conical intersection (CI), which is the crossing point of multidimensional electronic potential energy surfaces, is well established as a controlling factor in the initial steps of chemical dynamics of energetic molecules following their electronic excitations. In this article, we have presented different aspects of the ultrafast unimolecular relaxation dynamics of energetic molecules through CIs. For this task, we have employed ab initio multiple spawning (AIMS) simulation using the complete active space self-consistent field (CASSCF) electronic wavefunction and frozen Gaussian-based nuclear wavefunction. The AIMS simulation results collectively reveal that the ultrafast relaxation step of the best energetic molecules (which are known to exhibit very good detonation properties) is completed in less than 500 fs. Many, however, exhibit sub-50 fs dynamics. For example, nitro-containing molecules (including C-NO2, N-NO2, and O-NO2 active moieties) relax back to the ground state in approximately 40 fs through similar (S-1/S-0) CI conical intersections. The N-3-based energetic molecule undergoes the N-2 elimination process in 40 fs through the (S-1/S-0) CI conical intersection. Nitramine-Fe complexes exhibit sub-50 fs Fe-O and N-O bond dissociation through the respective (S-1/S-0) CI conical intersection. On the other hand, tetrazine-N-oxides, which are known to exhibit better detonation properties than tetrazines, undergo internal conversion in a 400-fs time scale, while the relaxation time of tetrazine is very long (about 100 ns). Many other characteristics of sub-500 fs nonadiabatic decay of energetic molecules are discussed. In the end, many unresolved issues associated with the ultrafast nonadiabatic chemical dynamics of energetic molecules are presented. Published by AIP Publishing

Adsorption and decomposition of monopropellant molecule HAN on Pd(100) and Ir(100) surfaces: A DFT study

We have performed density functional theory calculations with the generalized gradient approximation to investigate the catalytic decomposition reactions of one of the most promising monopropellants, hydroxylammonium nitrate (HAN), on two catalytically active single crystal Pd(100) and Ir(100) surfaces, aiming at exploring different reaction pathways and reactivities of these two surfaces towards the catalytic decomposition of HAN. We find that the HAN molecule binds both the Pd(100) and Ir(100) surfaces molecularly in different orientations with respect to the surface. The HONO elimination is found to possess the lowest activation energy on the Pd(100) surface; whereas, NO2 elimination is predicted to show the lowest activation energy on the Ir(100) surface. Exothermicities associated with different reaction steps are also discussed. This is the first theoretical report on the catalytic decomposition reactions of the HAN molecule on the single crystal Pd(100) and the Ir(100) surfaces using the periodic DFT calculations. (C) 2016 Elsevier B.V. All rights reserved

CO Activation Determines Ultrafast Dynamics of CO Oxidation Reaction on Pd Nanoparticles

Femtosecond two-pulse correlation spectroscopy, temperature program desorption spectroscopy, and density functional theory calculations are used to elucidate the mechanisms and the ultrafast dynamics of carbon monoxide (CO) oxidation reaction on palladium nanoparticle (Pd NP) surfaces. Two different time scales for the CO oxidation reaction on Pd NPs are observed: a fast channel (time constant ∼7 ps) is found for the oxidation reaction when strongly bound CO is involved, and a slow channel (time constant ∼15 ps) is found for the oxidation reaction when weakly bound CO is involved. Temperature-programmed desorption spectroscopy confirms that the fast and the slow channels are associated with CO oxidations mostly on (111) facets and at edges of the Pd NPs, respectively. This is the first report on heterogeneous gas-phase ultrafast dynamics study of CO oxidation reaction on transition metal (which is an active catalyst in catalytic converter) NP surfaces