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
