Energy-Efficient Time-Based Encoders and Digital Signal Processors in Continuous Time

Continuous-time (CT) data conversion and continuous-time digital signal processing (DSP) are an interesting alternative to conventional methods of signal conversion and processing. This alternative proposes time-based encoding that may not suffer from aliasing; shows superior spectral properties (e.g. no quantization noise floor); and enables time-based, event-driven, flexible signal processing using digital circuits, thus scaling well with technology. Despite these interesting features, this approach has so far been limited by the CT encoder, due to both its relatively poor energy efficiency and the constraints it imposes on the subsequent CT DSP. In this thesis, we present three principles that address these limitations and help improve the CT ADC/DSP system. First, an adaptive-resolution encoding scheme that achieves first-order reconstruction with simple circuitry is proposed. It is shown that for certain signals, the scheme can significantly reduce the number of samples generated per unit of time for a given accuracy compared to schemes based on zero-order-hold reconstruction, thus promising to lead to low dynamic power dissipation at the system level. Presented next is a novel time-based CT ADC architecture, and associated encoding scheme, that allows a compact, energy-efficient circuit implementation, and achieves first-order quantization error spectral shaping. The design of a test chip, implemented in a 0.65-V 28-nm FDSOI process, that includes this CT ADC and a 10-tap programmable FIR CT DSP to process its output is described. The system achieves 32 dB – 42 dB SNDR over a 10 MHz – 50 MHz bandwidth, occupies 0.093 mm2, and dissipates 15 µW–163 µW as the input amplitude goes from zero to full scale. Finally, an investigation into the possibility of CT encoding using voltage-controlled oscillators is undertaken, and it leads to a CT ADC/DSP system architecture composed primarily of asynchronous digital delays. The latter makes the system highly digital and technology-scaling-friendly and, hence, is particularly attractive from the point of view of technology migration. The design of a test chip, where this delay-based CT ADC/DSP system architecture is used to implement a 16-tap programmable FIR filter, in a 1.2-V 28-nm FDSOI process, is described. Simulations show that the system will achieve a 33 dB – 40 dB SNDR over a 600 MHz bandwidth, while dissipating 4 mW

Electrospray technique for cocrystallization of phytomolecules

Poor aqueous solubility of most of the phytomolecules has restricted their vital biological use. Cocrystal approach can be one of the remedies for the problem. The present work was carried out with an objective to screen the potential of electrospray technique towards cocrystallization of quercetin (QUE). QUE was cocrystallized with caffeine (CAF) and nicotinamide (NIC) as coformers. Saturated methanolic solutions of QUE with either of the coformers (CAF and NIC) in 1:1 ratio were electrosprayed at 40 °C. The technique was successfully used for cocrystallization of QUE with CAF and NIC separately as revealed by Powder X-ray Diffraction, Differential scanning calorimetry and Fourier transform infrared spectroscopy studies. Additionally, the results of saturation solubility study suggested 14 and 11 folds increase in solubility of QUE upon its cocrystallization with CAF and NIC respectively. Herein we propose a new technique for cocrystallization and in turn resolving solubility issues of phytomolecules which can be an alternative to the existing cocrystallisation techniques

QbD based approach for optimization of Tenofovir disoproxil fumarate loaded liquid crystal precursor with improved permeability

BCS class III drugs suffer from a drawback of low permeability even though they have high aqueous solubility. The objective of current work was to screen the suitability of glyceryl monooleate (GMO)/Pluronic F127 cubic phase liquid crystals precursors for permeation enhancement and in turn the bioavailability of tenofovir disoproxil fumarate (TDF), a BCS class III drug. Spray-drying method was used for preparation of TDF loaded liquid crystal precursors (LCP) consisting of GMO/Pluronic F127 and lactose monohydrate with an ability to in situ transform into stable cubic phases upon hydration. The quality by design (QbD) approach (Factorial design) was used for batch optimization. Spherical TDF loaded LCP as revealed by scanning electron microscopy photographs when hydrated and analyzed by small angle X-ray scattering confirmed formation of cubic phase. Differential scanning calorimetry and X-ray diffraction studies confirmed the molecular dispersion of TDF in polymer matrix and also suggested the conversion of TDF from crystalline to amorphous form. In vitro TDF release from prepared LCP showed controlled drug release over a period of 10 h. Further ex vivo studies revealed permeation enhancing activity of prepared LCP, which was highest when tested in presence of digestive enzyme extract. Thus, formulation of stable liquid crystal powder precursor can serve as an alternative for designing oral delivery system for drugs with low permeability

Potentiating antimicrobial efficacy of propolis through niosomal-based system for administration

Background: Propolis is a multicomponent active, complex resinous substance collected by honeybees (Apis mellifera) from a variety of plant sources. This study was designed to improve the antimicrobial efficacy of propolis by engineering a niosomal-based system for topical application. Methods: Propolis was extracted in ethanol and screened for total polyphenol content. Propolis-loaded niosomes (PLNs) were prepared with varying concentrations of Span 60 and cholesterol. The PLNs were evaluated for physicochemical parameters, namely, vesicle size, entrapment efficiency, zeta potential, surface topography and shape, and stability, followed by screening for in vitro antimicrobial activity. The PLNs were formulated into propolis niosomal gel (PNG) using Carbopol P934 base and subjected to ex vivo skin deposition study. Results: The ethanolic extract of propolis had high polyphenolic content (270 ± 9.2 mg GAE/g). The prepared PLNs showed vesicle size between 294 nm and 427 nm, and the percent entrapment in the range of 50.62–71.29% with a significant enhancement in antimicrobial activity against Staphylococcus aureus and Candida albicans. Enhanced antimicrobial activity of PLNs was attributed to the ability of niosomes to directly interact with the bacterial cell envelop thereby facilitating the diffusion of propolis constituents across the cell wall. The formulated PNG exhibited a twofold better skin deposition due to improved retention of niosomes in the skin. Conclusion: The findings indicate that the engineering of a niosomal-based system for propolis enhanced its antimicrobial potential through topical application

Fabrication, optimization and characterization of an osmotic push-pull drug delivery system for paliperidone

الملخص: أهداف البحث: باليبيريدون هو عقار نظام تصنيف الصيدلة الحيوية الدرجة الثانية ذو قابلية منخفضة للذوبان ونفاذية عالية. يحتوي على 28 ٪ من التوافر الحيوي عن طريق الفم المطلق ونصف عمر التخلص منه 23 ساعة. من أجل تحقيق إطلاق متحكم به على مدى فترة طويلة من الوقت بجرعة منخفضة وتجنب الحاجة إلى جرعة تحميل، يباع الجهاز اللوحي ثلاثي الطبقات التناضحي الدفع والسحب حاليا في السوق. ومع ذلك، فإن الأجهزة اللوحية ثلاثية الطبقات لها عيوب عديدة مثل العملية المعقدة وتكلفة الإنتاج العالية وصعوبة تحقيق توحيد المحتوى. وبالتالي كان الهدف من هذه الدراسة هو التغلب على الصعوبات المذكورة أعلاه المرتبطة بالريسبيريدون وصياغة قرص ثنائي الطبقة له خصائص دوائية مماثلة لتلك الخاصة بالعقار المرجعي إنفيجا. طريقة البحث: تم تحضير الأقراص ثنائية الطبقة عن طريق تحسين اللب والغشاء شبه المنفذ. تم تحليل التأثير الإضافي لوقت المعالجة مع حجم وعدد الفتحة على ملف الذوبان للأقراص المعدة. تم استخدام درجتين مختلفتين من أكسيد البولي إيثلين في الطبقة الأساسية وطبقة الدفع كمشكلين للمسام. النتائج: كانت قيم اختلاف الوزن والقابلية للتلف والصلابة للأقراص المحضرة ضمن حدود الخلاصة. كانت المعلمات المحسنة ثنائية الطبقة للقرص المحضر هي وقت المعالجة 5 ساعات، وطبقة الختم 7٪ وزن/وزن، وغطاء ''إي آر'' 13% وزن/وزن، وحجم الفوهة 0.6 مم، وعدد الفوهة -02. أظهرت صياغة أخرى للأقراص قيمة ''إف 2'' تبلغ 75.67 مما يشير إلى أن ملف تعريف الذوبان الخاص بها مشابه للدواء المرجعي إنفيجا. الاستنتاجات: وهكذا في العمل الحالي، تم إعداد قرص ثنائي الطبقة من الباليبيريدون للتغلب على العيوب المرتبطة بالتركيبة المسوقة بنجاح، مما يوفر مزايا مثل عملية تحضير أبسط، وفعالية من حيث التكلفة، وإعداد أقل استهلاكا للوقت للب القرص. Abstract: Objectives: Paliperidone is a BCS class II drug with low solubility and high permeability. It has 28% absolute oral bioavailability and an elimination half-life of 23 h. An osmotic push–pull trilayer tablet currently available on the market has achieved controlled release of a low dose over an extended time period, while avoiding the need for a loading dose. However, this trilayer tablet has several disadvantages, such as complicated processing, high production costs and difficulty in achieving uniformity of the contents. Thus, the objective of this study was to overcome the above difficulties associated with paliperidone and to formulate a bilayer tablet with a similar drug profile to that of the reference listed drug Invega®. Methods: The bilayer tablets were prepared by optimization of the core and semi-permeable membrane. Effects of the curing time, and the size and number of orifices on the prepared tablets’ dissolution profile were analyzed. Two different grades of polyethylene oxide were used in the core and push layer as pore formers. Results: The weight variation, friability and hardness values of the prepared tablets were well within compendium limits. The optimized bilayer parameters for the prepared tablets were curing time, 5 h; seal coat, 7% w/w; ER coat, 13% w/w; orifice size, 0.6 mm; and orifice number, 2. Further tablet formulation resulted in an F2 value of 75.67, indicating a dissolution profile similar to that of Invega®. Conclusion: Bi-layer tablets of paliperidone overcoming the drawbacks of the marketed formulation were successfully prepared, and offer advantages such as a simpler preparation process, cost effectiveness and faster preparation of the tablet core