cpe280 Flashcards
What is Pharmaceutical engineering
is a field that deals with the process of creating pharmaceutical products such as medicines.
They also help to produce regulatory guidelines regarding the production of medical drugs
What is biopharmaceutical engineering
A field that deals with the process of a biological medicinal product which is a pharmaceutical drug product manufactured from biological sources
What is the difference between biopharm and pharm
- method by which they are produced
bio- produced from living organisms
pharm - series of chemical synthesis
what is biological engineering
the application of principles of biology and engineering to create products of value to society
unit operations
- fermentation
- cell culture reactors
- centrifugation
- filtration
- chromatography
- crystillisation
- solvent extraction
- precipitation
engineering
- scale up
- materials
- useful maths to assist operation
types of organisms
- bacteria
- yeast
- fungi
- actinomycetes
- mammalian cells
low molecular weight drugs
small molecules-synthetic drugs
the first synthetic compound was synthesised by who
german chemist Justus von Liebig and was used as a sedative-hypnotic until 1869
what is the role of chemical engineering in pharmacy industry
- compounds are synthesised by chem eng processes
- the extraction of active ingredient from complex mixture of side products
- important part of chemical engineering is purification and mixing
- batch system so control systems are vital
sulphonamides
what are they?
who produced them?
the molecule was orginally part of a collection of azo dyes bio-converted to sulfanilamide in the body. (stops the growth of gram postive bacteria .)
sulphonamides mimic a precursor in folate biosynthesis and stops bacterial growth. can cause a wide range of diseases such as scarlet fever, pneumonia, meningitis and septicaemia.
Gerhard Domagk served as a medic in the german army, in the late 1920s he worked at testing bayers collection of azo-dyes as therapeutic agents against streptococcal infections.
penicillin
who discovered it?
what did penicillium mould do?
when was it available?
discovered by Alexander Fleming in 1928. Professor Harold tried to purify penicillin but failed. Ernst and Florey investigated natural antibacterial agents produced by microorganisms and revisited flemings work and discovered the properties and how to manufacture and purify it.
widely available in 1944
penicillium mould was producing something that suppressed bacterial growth
what did Howard Florey do in 1941 to help industrialise penicillin?
he flew to USA to get help and met with Andrew Moyers group USDA which developed liquid culture of penicillium and improved yields.
He also met with pfizer as they needed to design reactors that could produce penicillin, they knew how to run liquid fermentation processes. Maragret Rousseau american chemical engineer to design the first commercial penicillin production plant.
Typical media for developing liquid culture
Typical media • glucose (0-1 % w/w) • lactose (1-3 % w/w) • corn steep liquor (1-5 % w/w) • sodium nitrate (0-0.05 % w/w) • calcium carbonate (0-1 % w/w) • phenylacetate (0.01-0.1 % w/w)
corn steep liquor
is a waste product of ‘corn wet milling’ process where clean corn is soaked in water containing lactic acid and sulphur dioxide for 40 hours, the liquor is filtered then concentrated using evaporators.
what did Chaim Weizmann do?
The first world war demanded quantities of acetone for the manufacture of cordite used in artillery shells. Weizmann is the founding father of industrial microbiology and developed the ABE process which produces acetone.
the ABE process is anaerobic cultivation of clostridium acetobutylicum so needs no aeration and stirring is not critical.
how was ethanol fermented?
raw material was corn milled and the germ and bran extracted before adding to hot water. the corn mash inoculated and left for 2 days (will contain spores). continuous distillation resulted in 50% water, 30% butanol, 15% acetone and 5% ethanol.
transferred to kettle skills to produce pure buanol, acetone and 95% ethanol
how is citric acid made?
using a fermentation of aspergillus niger and is an aerobic process
what was the issue with growing penicillin in deep tanks and how was it solved?
it needs air to grow, aerating the fermentation in deep tanks presented a problem. Bubbling sterile air through the culture medium caused severe foaming. Squibb solved the problem by using an anti-foam to alter the surface tension and pop the bubbles.
oxygen transfer
- sparger:ncan be open tubes, perforated tubes, porous diffusers
- impellers: rushton turbine is a high shear impeller and breaks air bubbles down to a smaller size
- baffles
Genomes
the distance between bases along the DNA strands =0.3nm
for the human genome with its length of 3GBP it tells us that each of our cells has approx a metre of DNA, which is compressed into a nuclear volume with a radius of a few microns.
Plasmids
small circular, double - stranded DNA molecule that is distinct from a cells chromosomal DNA.
They naturally exist in bacterial cells and they also occur in some eukaryotes .
often the genes carried in plasmids provide bacteria with genetic advantages such as antibiotic resistance.
Genetic engineering
- isolate plasmid from bacterium
- isolate gene of interest from another cell
- insert gene of interest into plasmid (recombinant DNA)
- Bacterial cell takes up plasmid containing gene through a process called transformation
- bacterial cell divides along with the plasmid and forms a clone of cells.
what are amino acids
all proteins are composed of 20 amino acids.
Amino acids are amphoteric and zwitterionic
peptide bonds
condensation reaction of two amino acids
Charged polar side chains
basic aa are +ve charged at physiological PH
acidic aa are -ve charged at physiological PH
the 20 aa vary in properties including polarity, acidity, basicity, aromaticity, ability to cross link, ability to hydrogen bond and chemical reactivity.
Polypeptides
described starting at the amino terminus (N-terminus) and sequentially naming each residue until the carboxy terminus (C-terminus)
Primary structure
amino acid sequence in a polypeptide chain
Secondary structure
double helix
defined as the local conformation of its backbone.
tertiary structure
folding of secondary structure together with its spatial dispostions of its side chains
Quaternary structure
the four separate chains of hemoglobin assembled into an oligomeric protein
spatial arrangement of protein subunits
properties of proteins are determined by…
three dimensional structure
Central dogma
DNA–> RNA –> Protein
transcription
translation
Transcription
synthesis of RNA
unique nucleotide sequence of a gene is transcribed from DNA into a complementary nucleotide sequence in messenger RNA (mRNA).
mRNA carries the protein building instructions to the cellular machinery that synthesizes protein
Translation
polypeptide syntheis under the direction of mRNA
linear sequence of mRNA is translated into a sequence of amino acids in a polypeptide.
translation occurs on ribosomes they facilitate the orderly linking of amino acids into polypeptide chains
protein post translational modifications
increase the functional diversity of proteins, covalent addtion of functional groups, proteolytic cleavage
of regulatory subunits, or degradation of entire proteins.
commonly employed to regulate cell activity
Advantages of protein post translational modifications
occur at distinct amino acid side chains or peptide linkages and most often mediated by enzymatic activity.
Glycosylation
protein glycosylation is one of the major PTMs with significant effect on protein folding, distribution, stability and activity.
phosphorylation
reversible protein phosphorylation, principally on serine, threonine or tyrosine residues is the most important PTMs
play critical roles in the regulation of many cellular processes including cell cycle and growth
most common mechanism of regulating protein function and transmitting signals throughout the cell
only occurs at the side chains of three amino acids in eukaryotic cells.
what is pharmaceutics
A branch of pharmacy which includes the study of, formulation of drugs into a dosage form
A systematic approach to get an effective and stable formulation without disturbing its quality and deals with the technology involving large scale manufacturing
What is a drug
A chemical entity obtained from various source which produces therapeutic effect on the body
physical Pharmaceutics
rheology diffusion aggregation surface tension adhesion
Biological Pharmaceutics
nanoparticle flow
diffusion invivo
bioadhesion
movement in tumours
Dosage form
drugs are combined with other inert substances and converted into a suitable form of adminstration into body e.g. capsules, injections and tablets
Active Pharmaceutical Ingredients
Chemical compound that are actually used for diagnosis treatment and prevention of disease
excipients
Substances used to give particular shape to the formulation, to increase stability, platability and to make preparation more elegant
Excipient types?
coloring agent sweetening agent Flavouring agent Solubilizing agents antioxidants preservatives binding agents
What is Pharmacopoeia
legal and official book issued by recognised authority appointed by government of each country.
Comprimises of:
- a list of pharmaceutical substances, formulae along with their description and standards
What is Physical Pharmacy
study of physiochemical properties of a drug, additives, solvents and their application in the development of dosage form.
Includes the study of micrometrics, rheology and interfacial tension
What is biopharmaceutics
is the relationship between the physicochemical properties of a drug in a dosage form and observed therapeutic response after administration
what are biopharmaceutical methods
application of knowledge of drug release and transport across biomembranes to obtain/predict therapeutic affect from a product on administration to a patient
Biopharmaceutical factors influence the:
- protection and stability of the drug within the product
- rate of drug release from the product
- rate of dissolution of the drug at the absorption site
- availability of the drug at its site of action
factors related to drug instability
- chemical degradation of the active drug
- toxicity of the degradation product (hydrolysis, oxidation and photolysis)
- decrease in the product bioavailability
- change in the physical appearance in the dosage form
Factors that can improve protein stability
- optimisation of pH
- choice of solvent
- temperature
- ionic strength
Environmental factors during dissolution
- intensity of agitation
- concentration gradient (difference in concentration between solubility of the drug in dissolution media and average conc of bulk fluid)
- composition of dissolution medium (pH, ionic strength, viscocity are determined by the compostion of the medium)
- temperature of the dissolution medium
Factors affecting solubility
- polymophism
- amorphous state
- free acid
- particle size
- surfactants
Factors relating to the composition and method of manufacture for tablets and capsules
Tablets - amount type of diluent - type of tablet - granule size and size distribution -compression force Capsules - amount type of diluent - granule or powder size
Enviromental factors involved with dosage forms
- humidity during manufacture
- storage conditions for the dosage form
- age of the dosage forms
organic diluents
starch, lactose promote dilution of poorly water soluble.
inorganic diluents
dicalcium phosphate divalent calciumtetracycline complex- poorly soluble
lubricants
use to ensure good flow property of granules and reduce the sticking of particle to dyes
Granulating agents
used to hold a powder together in granulation, to promote the cohesive compact for directly compressible material
surfactants
used as wetting agent, solubilizes
colorants
may decrease the dissolution rate of crystalline drug by absorption onto crystalline face.
properties of collodial dispersion
- particle shape
- diffusion and sedimentation
- light scattering
- viscocity
- gel formation
- electric properties
wet granulation
has been shown to improve the wettability of poorly soluble drugs by incorporating hydrophillic properties into the surface of granules resulting in a greater dissolution rate
beaker methods
- rotating basket appratus (100RPM)
- rotating paddle apparatus ( paddle is vertically attatched to variable speed motor 50RPM)
- paddle over disk method
factors influencing the time course of drug in plasma
- physical and chemical properties of the drug
- type of dosage form of the drug
- compostion and method of manufacture of the dosage form
- site of absorption of the administered drug
- type of food taken by the patient
- age of patient
genetic compostion of the patient
bioavailability
transfer of drug from its site of administration into the body system
psychological factors influencing drug absorption
Nature of cell membrane
- semi - permeable: permits only water
- highly charged molecules and large molecules
physicochemical factors influencing drug absorption
surface area of the drug
salt form
state of hydration
solubility
dosage form factors influencing drug absorption
- rate of administration
- the inert ingredients
what is ADME
An acronym in pharmacology of adsorption, distriubution, metabolism and excretion and describes the dispostion of a pharmaceutical compound within an organism
what is adsorption
process which drugs enter the body
metabolism
irreversible transformation of patent drug compounds into daughter metabolites
why are dissolution tests important
tests binding of tablets and capsules
what is collodial dispersion
is a mixture of two substances, one in the dispersed phase and other in the continous phase
What is pharmaceutical analysis
the application of analytical procedures used to determine the purity, safety and quality of drugs and chemicals
examples of pharmaceutical analysis
- titration
- spectroscopic techniques
- chromatographic methods
- spectrometry
importance of pharmaceutical analysis
- identification of a drug in the formulated product
- determination of active ingredient or addtional impurities
- stability of the drug
- concentration of specified impurities
concentration of drug in plasma
types of chemical analysis
qualitative - preformed to establish compostion of natural substances, preformed to indicate whether substance is present in the sample
quantative - mainly used to quantify any substance in the sample
Instrumental methods (quantative)
- volumetric methods: acid base, redox, precipitation and complexmetric
- spectral analysis: colourimetry, UV visible, Infared, NMR and mass
- chromatographic techniques (planar, column)
- electrochemical methods; cell lysis
- Hyphenated techniques : GC-MS, LC-MS
what is colourimetry
used to determine the concentration of a solution having colour, uses fixed wavelengths which are in the visible range
what is spectrophotometry
measures how much light a chemical substance absorbs, by measuring the intensity of light (uses UV and IR)
what is Infrared spectroscopy
interaction of infrared radiation with matter to identify and study chemical substances
What is Liquid chromatography
affinity of analyte as it passes through mobile phase. Liquid analyte is used
What is Gas chromatography
used for analytes that can be vapourised without being decomposed
what is HPLC chromatography
reservoir –> pump –> injector –> column –> detector –> data system
mobile- non polar
stationary - polar
what is size exclusion chromatography
large particles can not enter the pores of stationary phase (elute faster)
what is ion exchange chromatography
ionic compounds are separated together with inetractions of ions
what is Affinity chromatography
bind, wash and elute
examples of non instrumental methods
- Bioloigical methods: in vitro, animal studies and microbiological assays
What is microbiology
the study of living organisms of microscopic size which include bacteria, fungi and viruses.
what does microbiology deal with
deals with the form, structure, reproduction, physiology and classification of microrganisms
Examples of microbiology
wine making, penicillin production
what is pharmaceutical microbiology
involves the study of microorganisms associated with the manufacture of pharmaceuticals.
examples of pharmaceutical microbiology
minimizing the number of microorganisms in a process environment and ensuring the finished pharmaceutical product is sterile
what is industrial microbiology
production of medicinal products such as antibiotics and vaccines, fermented beverages, industrial chemicals, production of proteins and hormones by genetically engineered organisms
what is good manufacture practice (GMP)
the production and testing practice that helps to ensure a quality production
why is GMP required
- to minimize human error
- to prevent the contamination of pharmaceuticals
- to ensure high quality of production
GMP guidelines
- Personnel protection equipment
- environment: control air, temp and humidity
- Equipment: must be cleaned and stored
Validiation: to ensure stability and conformity
Microbial tests for pharmaceuticals
- Microbial limit test
- Sterility testing
- Bacterial Endotoxin tests
- Growth promotion test
- Water Microbiological analysis
- Microbial identification
what is microbial limit test
(bioburden testing)
used to estimate the total number of viable organisms. the microbial content of the product includes the total bacterial count, total yeast and mold count
what is bacterial endotoxin(LAL testing)
endotoxins are natural compounds released by the cell wall of gram negative bacteria and are potentially toxic to humans.
The test for bacterial endotoxins is used to detect or quantify endotoxins using LAL which is an extract of blood cells from horse shoe crab.
Growth promotion test
quality control test of media measuring the ability of any media used to support growth when the inoculum contains a small number of microrganisms
Ecology of microorganisms as it affects the pharmaceutical industry
- atomosphere
- water
- skin
- raw materials
- packaging
- equipment
contamination
- microbial spoilage
- infection risk
- contamination control
types of microbial assays
- agar plate diffusion assay
- rapid reliable reproduciible microbial assay method
