Physical Characterization of Nano Particulates Used in the Pharmaceutical Industry

Introduction

The formal definition of nano particle is a discrete entity that has a dimension of 100 nm or less. A nano-scaled material, on the other hand, may be comprised of nano-scaled structures, though the physical dimensions of the material may exceed 100 nm. A spray-dried agglomerate of nano-sized particles would be described as nanoscaled. For pharmaceutical applications, one does not resort to the use of nano materials unless there is a therapeutic driving force to do so. If the compound is poorly soluble in-vivo or if the molecule is highly potent, and the desired presentation of the drug product is a tablet, capsule, or suspension, the decision may be implemented to produce the active pharmaceutical ingredient as a nano material.

The actual form of the nano materials covers a number of technologies, from actual nanocrystals, to emulsions, to liposomes. Regardless of the formulation or carrier, once this size range is implemented, the drug product performance is intimately connected to the physical properties of the active pharmaceutical ingredient. Physical characterization becomes a crucial part of the drug substance and drug product control strategy.

Physical Characterization Techniques

Sample Preparation

To obtain accurate and meaningful particle size data, the challenge for nano materials lies in the sample preparation. Because the material is so small and so surface active, generally accepted scientific practices can often end up producing artifacts, or altering the sample during measurement.

Toxicity concerns for highly potent nanocrystals suggest that the material should not exist as a dry powder, but can be more safely handled dispersed in a liquid. To prevent particle aggregation, either the pH can be adjusted, or surfactants can be used. Solubility of drug substance particles, however, is often pH dependent; therefore, if the pH is adjusted to provide adequate particle dispersion, the material could dissolve. The same phenomenon can occur with surfactants, where the particles can be solubilized by their addition.

If the particles are not solubilized by the use of surfactants, then for some characterization techniques, the adsorbed layer of surfactant will skew the particle size, making the particles appear larger. This, however, may be relevant to the performance of the drug, and such measurements can be valuable in predicting in vivo performance. Factors such as these must be considered when interpreting physical characterization data for nano materials in pharmaceutical applications.

Particle Size Measurement Via Dynamic Light Scattering

 Nano particle with adsorbed surfactant layer. Particle size data obtained by PCS will also measure the effect of the surfactant

Laser diffraction, the dominant platform for sizing most pharmaceutical powders, is an ensemble technique (i.e. measures many particles rather than a single particle measurement) that has a lower size limit of approximately 0.1 μm. To measure objects below that limit, dynamic light scattering (DLS), also known as photon correlation spectroscopy (PCS), is one of the few ensemble techniques that can be employed in this size range (0.005 – 1 μm). The technique is well established and several commercial platforms are available. 

Stable, well-dispersed particles are placed in the sample cell, where Brownian motion causes the particles to move randomly in the suspension. A laser beam passes through the sample cell and is scattered by the particles. The randomly changing diffraction pattern is converted into a histogram of intensity vs. size. Note that this data representation is not what one typically encounters, which is frequency vs. time. For this reason, PCS should be used to measure an average particle size rather than to produce a particle size distribution.

Particle Size Measurement by Electron Microscopy

Since the inception of nano technology, electron microscopy has served as the gold standard for measuring particle size and morphology. Initially, scanning electron microscopes were incapable of imaging nano-scaled objects; therefore transmission electron microscopy was the only microscopic technique available. With the advent of field emission electron guns for scanning electron microscopes, this scenario changed. Both instruments now offer clear images of nano materials. Figure 2 shows a scanning electron micrograph of drugcarrying biodegradable nanoparticles comprised of a polysebacic acid core and a shell of polyethylene glycol. 

Scanning electron microscopy offers a three-dimensional representation of the particles. The gray scale produced in SEM images, however, makes quantitative measurements on these images using appropriate image analysis software very difficult because of the lack of contrast provided.

For both transmission and scanning electron microscopy, the particles must be isolated, and are analyzed in a high vacuum environment.

Both techniques are insensitive to adsorbed surface layers such as surfactants that would be required to disperse the particles in a liquid (typically aqueous) environment.

To obtain these high resolution images, in both instances, the sample is bombarded with a very high energy electron beam. Prolonged exposure of the particles to this beam can cause degradation. This must be considered when opting for this type of analysis.

In summary, both PSC and electron microscopy provide information on particle size. If at all possible, both techniques should be employed for the size characterization of pharmaceutical nanoparticles. They are complimentary orthogonal techniques that provide valuable information.

Surface Area Measurements

Transmission electron micrograph of silica particles used for drug delivery

Particle diameter is perhaps the most relevant data to collect for scenarios where the physical size of the particle controls the in vivo performance of the drug product. When nano-scaled formulations are considered based upon the poor solubility of the drug substance, surface area measurement provides equally meaningful data. It has long been realized that surface area controls the dissolution of solid oral dosage forms. 

Because nanoparticles can easily pass through the filters and frits found in commercial surface area instruments, either the sample must be exposed to vacuum very slowly, or the material should be presented in an agglomerated form (i.e. nano-scaled). If the nanoparticles are contained in aggregates, a two-tiered strategy for characterization could be adopted, whereby the particle size measurement would measure aggregate size, and surface area measurements would provide an indication of the nano particle size. Often, high energy sonication is employed in an attempt to attain the primary particle size. This is not a preferred choice. The data obtained is often an indication of the degree of sonication, rather than the primary particle size.

by

Akshaya Srikanth,  Ronald Iacocca

Pharm.D Internee, Professor of Advanced Pharmaceutical Technology

Hyderabad, India

Centre yet to disburse funds for state's 18 pharmacovigilance at govt medical college hospitals

The Union government is yet to provide the funding, staff and infrastructure to commission the 18 Centres for Pharmacovigilance at government medical college hospitals in Karnataka.

Pharmacovigilance prevents adverse drug reactions. The Centres will monitor and evaluate the information from hospitals on Adverse Drug Reactions (ADRs) besides identifying information on drug hazards to ensure the safety of patients.

In early 2010, following the need to open up pharmacovigilance across the country, the erstwhile Drugs Control General of India (DCGI) Dr Surinder Singh was working to approve the Centre for Pharmacovigilance at  government hospitals attached to the medical colleges.

This led the Karnataka health and family welfare department to identify 16 locations which covers 12 government medical colleges hospitals  and six   government independent hospitals to establish the Centre for Pharmacovigilance. The state had also sent a letter of intent to these institutions.

The 12 colleges from the 10 districts are Bangalore Medical College and Research Institute, Government Dental College and Hospital, Bangalore,  Mysore Medical College and Research Institute (MMC&RI), Bellary Medical College now renamed as Vijayanagara Institute of Medical Sciences, Government Dental College and Research Institute, Bellary, Mandya Institute of Medical Sciences, Karnataka Institute of Medical Sciences, Hubli  which is attached to the Kempegowda Institute of Medical Sciences, Belgaum Institute of Medical Sciences (BIMS), Shimoga Institute of Medical Sciences(SIMS), Bidar Institute of Medical Sciences(BRIMS), Raichur Institute of Medical Sciences(RIMS), Hassan Institute of Medical Sciences (HIMS). The four hospitals are Jayadeva Institute of Cardiology, Indira Gandhi Institute of Child Health, Kidwai Memorial Institute of Oncology, Rajiv Gandhi Institute of Chest Diseases and SDS Sanatorium, Karnataka Institute of Diabetology, Karnataka Institute of Nephrology.

In fact in 2004, the  Director General Health Services (DGHS), Ministry of Health and Family Welfare received grant from the World Bank to start a  National Pharmacovigilance Programme for which Central Drugs Standard Control Organization (CDSCO) was the coordinator. Under the programme, 21 pharmacovigilance centres were opened with two zonal centres While  All India Institute of Medical Sciences, New Delhi covered North and East, the  KEM Hospital at Mumbai monitored southern and western regions in the country. There were five regional pharmacovigilance centres at Kolkata, Pondicherry (JIPMER), Nagpur and Mumbai with two centres. There were several periphery centres including Bangalore at the Victoria Hospital, Goa, and Mysore within JSS College of Pharmacy.

There are already a couple of similar centres run by pharmacy colleges in Karnataka which include the Drug Information Centre at Victoria Hospital supported by the Al Ameen College of Pharmacy.

“Since pharmacovigilance is now viewed as a critical component in patient care, we had  proposed to the DCGI on the need to set-up centres across healthcare providers in the state,” stated Dr BR Jagashetty, Karnataka drugs controller.

With India now recognized as a hub for human drug studies, an efficient pharmacovigilance programme is a must as stringent safety pharmacology  studies also help to prevent fatality and serious injuries of volunteers and patients who are part of the clinical trials, he added.

Source: PB

by

Akshaya Srikanth

Pharm.D Intern

Hyderabad, India

Why You Should Consider Pharm.D Programs

Different people have different career dreams. Just like any other career, pharmacy is not as easy as it seems. This is especially considering the fact that you will have to work really hard first before you can get your degree. Nevertheless, it is correct to say that every moment of it is worth your effort. This is because pharmacy offers you a wide range of career opportunities in the different health sectors.

Pharm.D simply refers to a six year doctorate program in pharmacy. Different countries have different policies and in some countries this is considered as a first professional doctorate degree in pharmacy and the grandaunts can be given the license to exercise their profession. The health care industry is very vital. A doctor of pharmacy is intended to prepare the students for different responsibilities as pharmaceutical care, research, pharmaceutical science and health policy and management among others.

With the many job opportunities contracted for this career, it is correct to say that the Pharm.D programs are one of the most marketable syllabuses globally. Positions are usually available in research facilities in different universities, hospitals, pharmaceutical companies, government agencies and advisory boards among many other places. Such programs will usually differ from the regular PhD which is usually theoretical to a research based degree.

You can get your doctorate in pharmacy from the different universities across the globe. While a simply degree in pharmacy is acceptable, today, more and more people would prefer to graduate with a Doctors in pharmacy especially due to the tight competition in the career opportunities available.

A Pharm.D degree is intended to equip you with all the knowledge necessary for any pharmaceutical field of practice. What is more, students are also endowed with the necessary health care skills which are going to come in handy once they start practicing.

by

Akshaya Srikanth

Pharm.D Internee

Hyderabad, India

Understanding and Management Of ECG

Clinical uses of ECG

Gold standard for diagnosis of arrhythmias                                               

Often an independent marker of cardiac disease (anatomical, metabolic, ionic, or haemodynamic)                    

Sometimes the only indicator of pathological process
Limitations of ECG
It does not measure directly the cardiac electrical source or actual voltages
It reflects electrical behavior of the myocardium, not the specialised conductive tissue, which is responsible for most arrhythmias
It is often difficult to identify a single cause for any single ECG abnormality

Cardiac Electrophysiology

Cardiac cellular electrical activity is governed by multiple transmembrane ion conductance changes
3 types of cardiac cells

Pacemaker cells     - SA node, AV node

Specialised conducting tissue-Purkinjie fibres

Cardiac myocytes 

Cardiac Ion Channels

They are transmembrane proteins with specific conductive properties

They can be voltage-gated or ligand-gated, or time-dependent

They allow passive transfer of  Na+, K+, Ca2+, Cl- ions across cell membranes

Cardiac Ion Channels: Applications

Understanding of the cardiac action potential and specific pathologic conditions

e.g. Long QT syndrome                        

Therapeutic targets for antiarrhythmic drugs 

e.g. Azimilide (blocks both components of delayed rectifier K current)

Mechanisms of Arrhythmias

Important to understand because treatment may be determined by its cause

1.Automaticity

Raising the resting membrane potential

Increasing phase 4 depolarization

Lowering the threshold potential

e.g. increased sympathetic tone, hypokalamia, myocardial ischaemia

2.Triggered activity    

from oscillations in membrane potential after an action potential

Early Afterdepolarization

Torsades de pointes induced by drugs

Delayed Afterdepolarization

Digitalis, Catecholamines

3.Re-entry

from slowed or blocked conduction

Re-entry circuits may involve nodal tissues or accessory pathways

Be Aware of Rabies Disease

 Rabies is a viral disease. The virus travels from the site of entry (the bite or scratch) via the nerves to the brain and spinal cord and eventually spreads to the salivary glands. In humans, once symptoms have developed it is invariably fatal (there are reports of one or two people surviving once symptoms had developed). Symptoms may start with itching or tingling at the site of the bite or scratch. These may then develop to include headache and fever progressing to paralysis, agitation, spasm of the muscles used for swallowing, delirium and convulsions.
Symptoms

The incubation period for rabies is typically 1–3 months, but may vary from <1 week to >1 year. The initial symptoms of rabies are fever and often pain or an unusual or unexplained tingling, pricking or burning sensation (paraesthesia) at the wound site.

As the virus spreads through the central nervous system, progressive, fatal inflammation of the brain and spinal cord develops.

Two forms of the disease can follow. People with furious rabies exhibit signs of hyperactivity, excited behaviour, hydrophobia and sometimes aerophobia. After a few days, death occurs by cardio-respiratory arrest.

Paralytic rabies accounts for about 30% of the total number of human cases. This form of rabies runs a less dramatic and usually longer course than the furious form. The muscles gradually become paralyzed, starting at the site of the bite or scratch. A coma slowly develops, and eventually death occurs. The paralytic form of rabies is often misdiagnosed, contributing to the underreporting of the disease.
Diagnosis

No tests are available to diagnose rabies infection in humans before the onset of clinical disease, and unless the rabies-specific signs of hydrophobia or aerophobia are present, the clinical diagnosis may be difficult. Post mortem, the standard diagnostic technique is to detect rabies virus antigen in brain tissue by fluorescent antibody test.

Transmission

Rabies can be transmitted in a number of ways to humans. Dog bites are by far the most common source of infection—though mostly in undeveloped countries where vaccination programs are not in place. A scratch to the skin, a lick on a fresh skin break or contact of the infected saliva with intact mucous membranes may also transmit rabies. Cats, bats, foxes, skunks, raccoons, monkeys and many other animals can be infected with this virus. Animals may be infectious for five days before they develop symptoms. More unusual routes of infection have also been documented. Aerosol transmission has been reported in a bat infested cave in South America and corneal transplants taken from undiagnosed rabies sufferers have also transmitted this infection to others. 

The incubation period for rabies in humans varies from 4 days to 7 years (usually between 20–90 days). The size and location of the bite or scratch, ie, proximity to the brain and the richness of the nerve supply to the area are thought to be important factors that influence the length of the incubation period. A deeply penetrating bite to the face or neck is likely to cause problems quicker than a scratch to the ankles.

Treatment and Prevention

Thoroughly cleanse all bites with soap and water and do not allow the wound to be stitched. Limited bleeding should be encouraged. Apply alcohol if possible. Once symptoms develop, death is inevitable in all cases. There is no cure. However, the disease can almost always be prevented, even after exposure, if rabies vaccine is administered without delay. Travelers should seek one of the modern cell culture vaccines. These can be difficult to obtain abroad. Some countries are using less effective locally produced vaccines that have to be administered into the abdomen; these are best avoided where possible. Travelers who have had a full course of pre-exposure vaccines still need to seek post exposure vaccines if they are bitten. However, they should only need two vaccines over 2 days and they will not need the human rabies immunoglobulin (HRIG) injection (HyperRAB S/D), which is in short supply in many countries. Those who have not had any pre-exposure vaccines or had an incomplete course of vaccine before travel should be given five post-exposure vaccines over 28 days plus the human rabies immunoglobulin (HRIG). 

The antibody response to the first post exposure vaccine is expected to be rapid in those who have been “primed” with any rabies vaccines before they travel (even if they have not had a full 3 dose course). As the incubation period of the disease can in rare circumstances be as short as 4 days, the vaccines should always be sought as soon as possible. However, as the incubation period can be as long as several years in exceptional circumstances, it is still worthwhile getting vaccines if you were bitten in a risk area some time ago. 

Never approach or handle animals you don't know, particularly if they are acting strangely. Pre-exposure immunization against rabies is recommended for long-stay travelers/residents and those who intend to travel to rural and remote areas in areas where rabies is common. In the event of a bite, your body's responses could be quickly activated by booster doses of vaccine. A full course of pre-exposure vaccines is three doses given on Days 0, 7 and 21–28. All travelers to risk areas should know what to do if they are bitten.

FIRST AID TREATMENT
Effective treatment soon (within a few days, but as soon as possible) after exposure to rabies can prevent the onset of symptoms and death.

Post-exposure prevention consists of local treatment of the wound, administration of rabies immunoglobulin (if indicated), and immediate vaccination.

Local treatment of the wound

Removing the rabies virus at the site of the infection by chemical or physical means is an effective means of protection. Therefore, prompt local treatment of all bite wounds and scratches that may be contaminated with rabies virus is important. Recommended first-aid procedures include immediate and thorough flushing and washing of the wound for a minimum of 15 minutes with soap and water, detergent, povidone iodine or other substances that kill the rabies virus.

Please watch this video

                                           

by

Akshaya Srikanth

Pharm.D*

Hyderabad, India
Please feel free to share your comments for my handwork

Career options for those with a degree in pharmacy

Most of us think of pharmacists as the persons who are behind the counter when we go to a drug store with a prescription. While retail pharmacy is a common career choice for pharmacists, there are many other options available to those who have completed their Pharm.D degree and the necessary licensure requirements. Although there are a variety of practice settings, compensation remains relatively consistent across all of these employment options with minor variations according to hours of work and call.

Here are the some career options in this field:

Retail Pharmacy/ Chemists 

A pharmacist in medical retail store prepares and dispenses drugs on prescription to the general consumer. With the growing availability of pre-packaged doses, the pharmacists now monitor the drug sale on the basis of prescriptions and dosage and give over-the-counter advice on how to use the prescribed drugs.

In the retail sector pharmacists run chemist's shops. As medical representatives, they inform and educate medical practitioners about the potential uses of the drug or health product and its administration along with the side effects or precautions for its use. The job entails regular visits to medical practitioners, hospitals, clinics, nursing homes, health centres. There is usually a lot of touring to be done in this case.

Hospital Pharmacy

The primary role of a hospital pharmacist is to provide medication and medication management services to patients who are hospitalised or are visiting hospital-based clinics, and to provide medication services to health professionals who care for patients in the hospital set up.

Hospital pharmacists have exposure to many complicated and unique therapy needs, including intravenous medication therapy, nutrition, and the specific needs of newborns and the elderly. Pharmacists in the practice find working with other health professionals, work variety and focused clinical care opportunity rewarding. This is the second most common practice area.

Industrial Pharmacy 

While most firms are involved in the production of pre-formulated preparations, a growing number of firms are developing new formulations through autonomous research work. Industrial pharmacists carry out clinical trials, where drugs are tested for safety and effectiveness work in research and development to develop new formulations the production job entails management and supervision of the production process, packaging, storage and delivery work in marketing, sales and quality control.

In addition to the many opportunities for graduates in the many areas of pharmacy practice there are increasing numbers of opportunities within the pharmaceutical industry in advanced and specialised areas, as the depth and breadth of education in pharmacy increases opportunities in industry. This includes the promotion of pharmaceuticals to health professionals, marketing, development of new drugs and dosage forms, clinical studies in patients, monitoring pharmaceutical use on a population scale, and managing regulatory and legal issues.

Government Services

Pharmacists are hired within the central and state government departments - the Health Protection Branch of the Department of Health and Welfare, the Pest Control Division of Agriculture, the Department of National Defense, Provincial Research Councils, and the Provincial Departments of Agriculture or Environment. There are employment opportunities available also within the food and cosmetic industries or within any other industry that requires an assurance that new products are as safe and effective as possible. In government departments, a pharmacist maintains proper records according to various Acts governing the profession.

Pharmaceutical Education 

Many pharmacists work as faculty in colleges of pharmacy. These pharmacists enjoy influencing the future of pharmacy by educating future pharmacists and may participate in direct patient care and/or scientific research as well. Academic pharmacist practice has its rewards in disseminating and discovering new ideas that change medication use, pharmacist practices and healthcare policy. Career as a teacher is satisfying as it allows interaction with people, especially students, and provides them with the flexibility to pursue their own ideas in the field.

Nuclear Pharmacy 

Nuclear pharmacists are responsible for measuring and delivering radioactive materials which are used in digital imaging (MRI, CT, etc) and other procedures in medical offices and hospitals. Due to the nature of the radioactive materials and how they are handled, nuclear pharmacists are typically required to start each work day very early, sometimes pre-dawn, as the radioactive materials must be delivered within a few hours of their use, or they lose their effectiveness

Clinical Research

Recently, Clinical research has also opened its door for B.Pharma graduates as medical underwriter, CRO, data validation associate, clinical research associate etc. A clinical research associate plays an important role in monitoring and overseeing the conduct of clinical trials, which are conducted on healthy human volunteers. They have to see that the trials meet the international guidelines and the national regulatory requirements.

Community pharmacy

The primary role of a community pharmacist is to provide medication and medication related services to patients. In most settings, pharmacists provide prescription drug services to their community of patients, working with the patients and a broad spectrum of healthcare providers to achieve the best possible healthcare outcome of medication.

Quality Control & analysis

A pharmacy graduate can play a crucial role in controlling product quality as an analytical chemist or a quality control manager. The Drug and the Cosmetics Act (1945), Rules 71(1) and 76(1) says that the manufacturing activity should be taken up under the supervision of a technical man whose qualification should be B PharmA, B Sc, B Tech or medicine with Bio-Chemistry.

Research and Development

New and expanding knowledge in healthcare and biomedical sciences provides tremendous opportunities for the pursuit of research careers for pharmacists. Graduates with Pharm.D degree can pursue a research career directly or go in for additional education either in the form of residency and fellowship training or in formal graduate programmes leading to the M.S. and Ph.D. degrees.

With a clinical focus one can be involved in the conduct and analysis of large-scale human drug studies in academic, industrial, and governmental settings. Pharmacists are also highly qualified to pursue additional training in business, public health, or pharmaceutical socioeconomics in order to become involved in research in drug utilisation, healthcare outcomes, and the provision of pharmacy services.

Sales and Marketing

Ambitious achievers with pleasant personality and good communication skills can opt for the job of Medical Sales Representative. Companies prefer pharmacy graduates for this job, as they have a good knowledge about the drug molecules, their therapeutic effects and the drug -drug interactions.

by

Akshaya Srikanth

Pharm.D Intern

Hyderabad, India

Central Nervous System Infections

Central nervous system infections are usually:

Blood-borne invasion; most common

(e.g. polioviruses or Neisseria meningitidis)

Invasion via peripheral nerves; less common      

 (e.g. herpes simplex, varicella-zoster, rabies)

Blood-borne invasion takes place across: 

     - blood-brain barrier (encephalitis)

     - blood-cerebrospinal fluid (CSF) barrier (meningitis)

Invasion via peripheral nerves:

* Herpes simplex virus (HSV) and varicella-zoster virus (VZV) present in skin or mucosal lesions travel up axons to reach the dorsal root ganglia. 

* Rabies virus, introduced into muscle tissues by:   

     - bite of a rabid animal 

   - It enters peripheral nerves and travels to CNS, to reach the neurons

Pathologic consequences of CNS infection

In CNS; viruses infect neural cells, sometimes showing a marked preference

Polio and rabies viruses invade neurons. CJD virus invades oligodendrocytes

Spread of infection is direct from cell to cell along established nervous pathways

Bacteria and protozoa induce brain abscesses 

Meningitis

* Meningitis is one of the most terrifying disease

* It can be fatal in hours

* Early symptoms resemble, self-limiting condition (flu and colds)

Most common causes of meningitis are:

  a) Bacterial infections (Septic meningitis) may result in death or brain damage. 

  b) Viral infections (Aseptic meningitis) usually resolve without treatment. 

Bacterial Meningitis (Septic Meningitis)

Pneumococcal, Streptococcus pneumoniae (38%)

Meningococcal, Neisseria meningitidis (14%)

Haemophilus influenzae (4%)

Staphylococcal, Staphylococcus aureus (5%)

Tuberculous, Mycobacterium tuberculosis

Viral Meningitis (Aseptic meningitis)

Etiological Agents: 

Enteroviruses, most common (Coxsackie and Echovirus)

Adenovirus

Arbovirus

Measles virus

Herpes Simplex virus

Varicella Zoster virus
by
Akshaya Srikanth, Sunil Jain*
Pharm.D Intern, *Chief Pharmacist
Hyderabad, India

Physiology of SLEEP

How do we Measure Sleep?Electroencephalogram (EEG) measures the electrical changes in the brain. The electrodes are placed on the scalp. The wavy lines recorded by the EEG are called brain waves.

Electrooculogram (EOG) measures the electrical changes as the eyes rotate in its socket. The electrodes are placed either above and below the eye or left and right of the eye. 

Electromyogram (EMG) measures the electrical changes generated during muscle contraction. The electrodes are placed under the chin. 

EEG, EOG and EMG are recorded simultaneously and the patterns of activity in these three systems provide basic classification for the different types of sleep.  

Placement of electrodes to determine EEG,EOG and EMG

Brain, eye and muscle wave in NREM sleep have greater amplitudes and lower frequencies as compared to REM and wakefulness. The amplitude increases continuously, while their frequency decreases correspondingly from the time a normal person falls asleep, till he or she reach the deepest NREM sleep. 

Classification of Brain Waves

EEG associated with sleep from the highest to the lowest frequency: 

Beta waves (β) The frequency of beta waves range from 13-15 to 60 hertz (Hz) and an amplitude of 30 microvolt (μV). Beta waves are associated with wakefulness. 

Alpha waves (α) The frequency range from 8 to 12 Hz and an amplitude of 30 to 50 μV. These waves are found in people who have their eyes closed and relax or meditating.

Theta waves (θ) Frequency in the range of 3 to 8 Hz and amplitude of 50 to 100 μV. These waves are related with memory, emotions and activity in the limbic system. 

Delta waves (δ) It ranges from 0.5 to 4 Hz in frequency and amplitude of 100 to 200 μV. Scientists had observed delta waves in deep sleep and in coma patients because normal and healthy adults will not show large amount of delta waves. 

    Flat-line trace occurs when no brain waves are present and this is the clinical sign of brain death. 

STAGES OF SLEEP

Sleep is characterized by two distinct cycles, 

NREM sleep. Non-Rapid Eye Movement Sleep (NREM) is further classified into 4 stages: 

Rapid Eye Movement Sleep (REM) sleep

Stages 3 and 4 in humans are homologous to animal sleep stage of slow-wave sleep (SWS). A normal human sleep cycle starts with NREM stage 1, stage 2, stage 3, stage 4 and progresses to REM. This cycle is repeated several times throughout the night (between 4 to 5 cycles). The duration for each cycle has been identified ranging between 60 to 90 minutes. The next section explains the characteristics of each of the four stages in detail. 

Circadian Rhythms

Circadian Rhythm is one of the several intrinsic body rhythms modulated by the hypothalamus. The suprachiasmatic nucleus sets the body clock to 24 hours and is modulated by light exposure. The retino-hypothalamic tract allows light cues to directly influence the suprachiasmatic nucleus. 

Circadian rhythm allows the brain to regulate periods of rest during sleep (equivalent to battery re-charging) and periods of high activity during the wakefulness (equivalent to battery discharging). The nadir of the rhythm is in the early morning. The downswing in circadian rhythm after the apex in early evening is thought to initiate sleep and maintain sleep overnight for full restoration by preventing premature awakening. The morning upswing then facilitates awakening and acts as a counterbalance to the progressive discharge of wake neuronal activity, enabling cognitive function throughout wakefulness.

DIA to organize 2-day conference on pharmacovigilance in Bengaluru on March 3 & 4

Drug Information Association (DIA) is organizing a two-day Pharmacovigilance conference in Bengaluru on March 3 and 4, 2012  The event will be held at The Park hotel. The theme of the event is  “Future Perspectives in Pharmacovigilance.’

The key objective of the event is to explain the current global safety reporting requirements for prescription and over the counter drugs.

There is also need to discuss the new pragmatic approaches to pharmacovigilance as proposed in the Council for International Organizations of Medical Sciences (CIOMS) working group. Over the two days, experts will deliberate and provide inspection program of regulatory agencies in the area of clinical safety from US and Europe, stated Kaushik Desai, director DIA India.

The key note speakers are from India and abroad. They are Dr YK Gupta, department of clinical pharmacology, All India Institute of Medical Sciences, Moin Don, executive director PVCON, Pharmacovigilance Consulting Services, Stewart Geary, vice president, and deputy director of Corporate Regulatory Compliance, Safety & QA, Eisai Co. Ltd and Dr Vivek Ahuja, director, Pharmacovigilance, Asia Pacific, Baxter Healthcare.

While Programme co-chairs are Moin Don and Dr Ahuja, the programme committee members constitute Dr BR Jagashetty, Karnataka drugs controller, Dr Gupta, Prof. Parathasarthy Gurumurthy, professor and head of the department of clinical pharmacy, JSS College of Pharmacy Medical College Hospital, Mysore, RK Giridhar, vice president, BPO Pharma Services, Accenture, Dr Chitra Lele, chief scientific officer, Sciformix Corp.

International speakers panel covers Dr Sidney Kahn, principal scientist, Sciformix Pharmacovigilance Services, Dr Sumit Munjal, consultant, (oncology), Global Medical Safety, Johnson & Johnson, a division of Janseen-Cilag Ltd., Johnson & Johnson, UK and Angela Pitwood, VP, Pharmacovigilance, Indipharm Inc. US.

Some of the topics are safety and management during early drug development programme, US &EU safety regulations upsides-New FDA Rule/ DSURs, safety and regulatory writing, medical device vigilance, panel discussion on Schedule Y and Empowerment to Ethics Committees(ECs) and Institutional Review Boards (IRBs), India: as pharmacovigilance outsourcing destination, safety during clinical trials through medical monitoring, integrating pharmacovigilance in medical and para medical curriculum., Utility of Cloud Computing in pharmacovigilance data base domain.

The organizers recommend that the conference should be attended by those from clinical research, risk management, compliance, medical information, regulatory affairs, academia and pharmacology.