Engineer Micro- and Nano-Sized Polymeric Particles for Drug Delivery Using Advanced Multivariate Statistical Tools

Particulate drug delivery systems are gaining considerable attention in recent years due to increasing advantages for an effective delivery of therapeutics. Application of advanced particle engineering technologies in polymeric drug delivery systems has shown to improve the efficacy of a drug substance by maintaining stable levels in the blood when compared to traditional parenteral drug products. However, development of these products is a complex multifaceted process with numerous challenges. Formulation development scientists need to comprehend and control a range of unit manufacturing operations along with the formulation composition for a successful product. Therefore, the objective of this project is to study the development of advanced micro-and nano-sized drug products with minimum number of experiments using multivariate statistical tools. Chapter 1 provides background and literature on various polymers used in drug delivery and particle engineering technologies to manufacture micro- and nano-sized drug products. It also provides a comprehensive overview on various multivariate statistical tools that could be applied in product development. Chapter 2 compares the capabilities of principal component regression (PCR) and multiple linear regression (MLR) to model and predict the impact of formulation and process parameters on the metronidazole benzoate–ethyl cellulose microsponge particle properties. The observations imply that MLR models showed relatively better predictability than PCR. Chapter 3 reports the aerosolization of sildenafil citrate loaded polymeric microparticles engineered using multivariate statistical tools by spray-drying (SD) and spray freeze-drying (SFD) processes. Particles engineered by both SD and SFD demonstrate good aerosolization properties. However, particles engineered by SD demonstrated relatively superior aerodynamic characteristics than SFD Chapters 4 and 5 reports gelatin nanoparticles (GNPs) engineered by desolvation using multivariate statistical tools. About 20-40% of the low molecular weight (25 kD) fraction could be eliminated by a desolvating ‘as is’ gelatin with acetone. Studies demonstrated statistically significant (p\u3c0.05) roles of gelatin solution pH and incubation times on the size and size distribution of the nanoparticles prepared by desolvation. Irrespective of gelatin grades, desolvated gelatins produced GNPs with significantly (p=0.0287) lower size when compared to ‘as is’ gelatins. It is highly recommended to use freshly prepared gelatin solution to attain GNPs of reproducible size. Overall, these experimental findings show that selection of statistical design for particle engineering is formulation and process dependent. Reproducibility of protein-based nanoparticles are greatly influenced by starting material properties and sample composition prior to synthesis. This study is anticipated to lay foundation for further exploration to develop a highly-controlled processing technologies to engineer polymeric particulate drug delivery systems

The Effects of Nonlinear Damping on the Large Deflection Response of Structures Subjected to Random Excitation

Effects of both nonlinear damping and large deflection stiffness are included in the theoretical analysis in an attempt to explain the experimental phenomena of aircraft panels excited at high sound pressure levels; that is the broadening of the strain response peak and the increase in modal frequency. Beams and symmetrically laminated plates subjected to acoustic excitation are considered in the analyses. The excitations are ergodic and Gaussian with zero mean. A polynomial containing both linear and nonlinear damping terms is considered as a damping model. Galerkin\u27s method is used to derive modal equations. Direct equivalent linearization is used to solve nonlinear differential equations which contain both nonlinear stiffness and nonlinear damping terms to determine mean square maximum deflection, mean square maximum strain and spectral density function of maximum strain for the structures. For beams, simply supported and clamped, three modes are considered in the analysis. Isotropic material is considered for beams. It is shown that the choice of linear damping is important for multiple modes analysis and has more influence on root mean square (RMS) strains than on RMS deflections. Nonlinear damping has maximum influence on the first mode and has considerable influence on deflection and strain and modal frequency. For laminated plates, simply supported and clamped, only single mode analysis is carried out. Immovable and movable inplane edge conditions are considered. Graphite/Epoxy is the material used. It is shown that small values of nonlinear damping coefficient have significant influence on panel RMS deflection and strains and modal frequency. It is identified that nonlinear structural damping causes the broadening behavior of the strain response peaks at high sound pressure levels. Nonlinear analysis (large deflection with nonlinear damping) would yield more accurate and realistic predictions on panel random response. And also it is shown that by the inclusion of nonlinear damping, the linearized frequencies and RMS deflections and strains will be more realistic. This analytical investigation will help to broaden the basic understanding of the role of nonlinear damping on random response of structures and lead to better sonic fatigue design criteria

Extreme events enhance phytoplankton bloom in the south-western Bay of Bengal

253-258A study on MODIS (Moderate Resolution imaging Spectroradiometer)-derived chlorophyll-a concentration data was carried out for 12 years (2003 to 2014), to know the reasons for two episodic phytoplankton bloom events occurred in 2005 and 2013. During the month of December 2005 and 2013, magnitude of the production increased to two to three times of climatological value over the south-western Bay of Bengal region. Reasons for the bloom were examined with the available satellite resources and it was identified that the strong cyclonic eddy, with long residence time, caused the increase of the production. This production intensified when cyclones passed through or were close to the eddy. The vertical mixing enhanced (2013) when very severe cyclonic storms passed through or moved close to the eddy compared to depressions passing over it which caused further intensification of the primary production

Mathematical Modelling and Analysis of Memristors with and without its Temperature Effects

In this paper the main goal is to study the principle structure and characteristics of single and multiple memristors and also the temperature effects. The complete analysis described here is done by using matlab Simulink. The relationship between the on resistance, off resistance and ionic mobility with respect to temperature has been analyzed and shown graphically.  The memristor can be used as a High speed switch and it can be used in non volatile computer memories due to its higher switching speeds

LEAKAGE POWER REDUCTION IN CMOS CIRCUITS USING LEAKAGE CONTROL TRANSISTOR TECHNIQUE IN NANOSCALE TECHNOLOGY

In CMOS circuits, as the technology scales down to nanoscale, the sub-threshold leakage current increases with the decrease in the threshold voltage. LECTOR, a technique to tackle the leakage problem in CMOS circuits, uses two additional leakage control transistors, which are self-controlled, in a path from supply to ground which provides the additional resistance thereby reducing the leakage current in the path. The main advantage as compared to other techniques which involves the sleep transistor is that LECTOR technique does not require any additional control and monitoring circuitry, thereby limits the area increase and also the power dissipation in active state. Along with this, the other advantage with LECTOR technique is that it does not affect the dynamic power which is the major limitation with the other leakage reduction techniques

Prevalence of coronary artery diseases in type 2 diabetic women

Background: There was increasing evidence that gender differences are important in epidemiology, treatment and outcomes of many diseases, relevant for non-communicable diseases.Methods: Study was conducted in Department of General Medicine, GSL Medical College. Patients who were admitted with type 2 diabetes were recruited in the study. Each patient was interviewed to obtain detailed history and examined thoroughly as per predetermined protocol, national diabetes data group and WHO diagnostic criteria was used. Myocardial infarction was diagnosed by convex ST segment elevation in corresponding leads (early) or QS complexes or abnormal Q waves i.e. Q waves of 0.04 seconds or more in width (or) 25% or more of the voltage of the R wave in the same lead or both in the corresponding leads (late) or T wave inversion in the corresponding leads (late). Statistical analyses were done by using SPSS software version 21.0. Chi-square test was used to assess the association between different categorical variables; p<0.05 was considered statistically significant.Results: Out of 250 participants, 97 were diagnosed as coronary artery disease (CAD), maximum between 51-60 years age group; the difference was statistically significant (p<0.05). The association between dyslipidemia and CAD was statistically significant (p<0.05). Out of 188 post-menopausal cases, CAD was diagnosed in 86 cases; out of the 62 non post-menopausal cases, CAD was diagnosed in 11 cases; The difference was statistically significant (p<0.05).Conclusions: In premenopausal women, the prevalence of CHDs are significantly higher when compared to postmenopausal women

Pharmacology of Traditional Herbal Medicines and Their Active Principles Used in the Treatment of Peptic Ulcer, Diarrhoea and Inflammatory Bowel Disease

The endocrine, exocrine and paracrine secretions of the gastrointestinal (GI) tract play a pivotal role in the digestion and absorption of food and orally administered drugs. The secretion of mucus by mucus-secreting cells protects the erosion of the gastric mucosa from the highly acidic gastric juice. The secretion of hydrochloric acid from parietal cells is regulated by acetylcholine, histamine and gastrin. Disturbances in secretory functions of the gastrointestinal tract can lead to several GI complications. Conventional therapies employ a range of drugs that have been pharmacologically well characterised. While these drug molecules are proven to be beneficial, the adverse effects and drug-drug interactions highlight the need for better treatment modalities for GI tract disorders

R16. Formulation and Evaluation of Doxorubicin HCl Nanoliposomes by Ethanol Injection Method

Corresponding author (Pharmaceutics and Drug delivery): Arun Kumar Kotha, [email protected]://egrove.olemiss.edu/pharm_annual_posters/1015/thumbnail.jp

Theoretical pKa prediction of the α-phosphate moiety of uridine 5′-diphosphate-GlcNAc

The pKa value of the α-phosphate moiety of uridine 5\u27-diphosphate-GlcNAc (UDP-GlcNAc) has been successfully calculated using density functional theory methods in conjunction with the Polarizable Continuum Models. Theoretical methods were benchmarked over a dataset comprising of alkyl phosphates. B3LYP/6-31+G(d,p) calculations using SMD solvation model provide excellent agreement with the experimental data. The predicted pKa for UDP-GlcNAc is consistent with most recent NMR studies but much higher than what it has long been thought to be. The importance of this study is evident that the predicted pKa for UDP-GlcNAc supports its potential role as a catalytic base in the substrate-assisted biocatalysis

Physical properties and solubility studies of Nifedipine-PEG 1450/HPMCAS-HF solid dispersions

Low-order high-energy nifedipine (NIF) solid dispersions (SDs) were generated by melt solvent amorphization with polyethylene glycol (PEG) 1450 and hypromellose acetate succinate (HPMCAS-HF) to increase NIF solubility while achieving acceptable physical stability. HPMCAS-HF was used as a crystallization inhibitor. Individual formulation components, their physical mixtures (PMs), and SDs were characterized by differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy (FTIR). NIF solubility and percent crystallinity (PC) were determined at the initial time and after 5 days stored at 25 °C and 60% RH. FTIR indicated that hydrogen bonding was involved with the amorphization process. FTIR showed that NIF:HPMCAS-HF intermolecular interactions were weaker than NIF:PEG 1450 interactions. NIF:PEG 1450 SD solubilities were significantly higher than their PM counterparts (p \u3c 0.0001). The solubilities of NIF:PEG 1450:HPMCAS-HF SDs were significantly higher than their corresponding NIF:PEG 1450 SDs (p \u3c 0.0001-0.043). All the SD solubilities showed a statistically significant decrease (p \u3c 0.0001) after storage for 5 days. SDs PC were statistically lower than their comparable PMs (p \u3c 0.0001). The PCs of SDs with HPMCAS-HF were significantly lower than SDs not containing only PEG 1450. All SDs exhibited a significant increase in PC (p \u3c 0.0001–0.0089) on storage. Thermogravimetric analysis results showed that HPMCAS-HF bound water at higher temperatures than PEG 1450 (p \u3c 0.0001–0.0039). HPMCAS-HF slowed the crystallization process of SDs, although it did not completely inhibit NIF crystal growth