Speaker 1: Imagine just like holding a standard over the counter headache
Speaker 1: pill right in the palm of your hand. It weighs
Speaker 1: practically nothing, you know, it just looks like this completely inert,
Speaker 1: simple white speck of chalk. Yeah, totally unassuming exactly, and
Speaker 1: you swallow it with a gulp of water, and then
Speaker 1: thirty minutes later you're throbbing headache just vanishes. It feels
Speaker 1: like magic, but the reality is far stranger. That tiny
Speaker 1: white tablet is actually a masterpiece of extreme engineering. Absolutely,
Speaker 1: It's carefully designed to run this gauntlet of destructive physical
Speaker 1: and biological environments inside you.
Speaker 2: It really is the ultimate example of invisible complexity. I mean,
Speaker 2: to truly understand how that medication functions, we can't just
Speaker 2: look at human biology. We have to look at the
Speaker 2: severe physical chemistry of the raw materials, the mechanical violence
Speaker 2: of the manufacturing process, and even like the quantum physics
Speaker 2: used to prove its purity.
Speaker 1: Well, welcome to a special custom tailored deep dive designs
Speaker 1: specifically for you. Whether you're a pharmacy student gearing up
Speaker 1: for your exams, or maybe a young professional navigating the industry,
Speaker 1: or just an insanely curious self learner. Consider this your
Speaker 1: ultimate masterclass.
Speaker 2: We are going to be tracking the entire life cycle
Speaker 2: of a medicine today.
Speaker 1: Yes, we are drawing exclusively from the comprehensive guide GPAT
Speaker 1: and Gate Pharmacy. We're going from raw powder to mass manufacturing,
Speaker 1: into the bloodstream, and finally into the analytical lab.
Speaker 2: And we are skipping all the rope memorization.
Speaker 1: Oh yeah, definitely. We want to understand the mechanisms, right,
Speaker 1: the why and the how behind the science. Okay, let's
Speaker 1: unpact this. Before a drug can heal you, it actually
Speaker 1: has to be built, and that starts at this molecular
Speaker 1: stage known as preformulation.
Speaker 2: Yes, so when a pharmaceutical company develops a new active ingredient,
Speaker 2: they're essentially dealing with.
Speaker 1: Bulkpowder, just big vats of powder.
Speaker 2: Exactly, and you have to characterize that powder before you
Speaker 2: could even think about putting it into machines. A critical
Speaker 2: distinction here is separating a drug's habit from its crystal. Wait.
Speaker 1: I always thought this were kind of the same.
Speaker 3: Thing A lot of people do.
Speaker 2: Actually, but the habit is simply the outer external appearance
Speaker 2: of the powder grain. Okay, but the crystal that is
Speaker 2: the internal three dimensional arrangement of the actual molecules.
Speaker 1: Which brings us to polymorphism.
Speaker 2: Right.
Speaker 1: Yeah, This is when the exact same chemical substance can
Speaker 1: exist in like multiple different crystalline forms.
Speaker 2: Dicisely, the building blocks are identical, but they're just stacked differently.
Speaker 1: It reminds me of carbon you know, stack carbon atoms
Speaker 1: one way and you get the soft graphite and a pencil.
Speaker 3: Oh, that's a great analogy.
Speaker 1: Yeah, and then stack those exact same atoms in a
Speaker 1: different geometric lattice and boom, you get a diamond. It
Speaker 1: makes total sense that if a drug changes its internal
Speaker 1: physical architecture, its medical properties might change too.
Speaker 2: Right. What's fascinating here is that the internal crystalline structure
Speaker 2: dictates the thermodynamics of the drug, specifically how easily it
Speaker 2: breaks apart and dissolves in water. Right. In polymorphism, we
Speaker 2: basically categorize them into two main behaviors. First is an
Speaker 2: antiotropic polymorphism.
Speaker 1: In antiotropic okay.
Speaker 2: Yeah, where one crystal form can reversibly shift into another
Speaker 2: form just by changing the ambient temperature or pressure. Elemental
Speaker 2: sulfur actually does this naturally.
Speaker 1: Wow, So the manufacturer has to be incredibly careful about
Speaker 1: the temperature of the factory floor then, or the drug
Speaker 1: might literally transform into a different structural version of itself.
Speaker 2: Exactly, which could completely render it insoluble in the human body.
Speaker 1: That's terrifying, right.
Speaker 2: And the second type is monotropic polymorphism, and this one
Speaker 2: is irreversible. One form is inherently unstable at all temperatures
Speaker 2: and pressures, and it will eventually just degrade into the
Speaker 2: stable form.
Speaker 1: Ah okay.
Speaker 2: Glycerl steerrates are a classic example of this. But to
Speaker 2: predict exactly when these structural shifts happen, formulation scientists rely
Speaker 2: on something called a van hoffplot.
Speaker 1: Yes, I was looking at these plots in the text.
Speaker 1: Instead of just guessing, they graph the log moolar solubility
Speaker 1: of the drug against the temperature. By tracking the solubility
Speaker 1: lines of two different polym morphs on the graph, you
Speaker 1: find the exact intersection point that transition temperature is where
Speaker 1: both forms have identical free energies, which.
Speaker 2: Is crucial because it gives the engineers a strict thermal
Speaker 2: boundary they cannot cross during manufacturing.
Speaker 1: That is so precise, But along with temperature, surface area
Speaker 1: is like perhaps the most heavily scrutinized metric.
Speaker 3: Isn't it.
Speaker 1: Oh?
Speaker 3: Absolutely.
Speaker 2: I mean the more surface area drug particle has, the
Speaker 2: faster the surrounding stomach fluid can interact with it and dissolve.
Speaker 1: It makes sense.
Speaker 2: We measure the raw size of the particles using stream
Speaker 2: counting devices like a culter counter or.
Speaker 3: An hia hiac right.
Speaker 2: Which basically monitor electrical or light changes as the particles
Speaker 2: flow through a tiny aperture. But for true surface area
Speaker 2: they use bt adsorption.
Speaker 1: Oh, the Bruneauer emmet Teller method. This is brilliant because
Speaker 1: I mean, you can't just use a tiny ruler to
Speaker 1: measure a microscopic, jagged grain of powder.
Speaker 3: No, you really can.
Speaker 1: Instead, they cool the sample down with liquid nitrogen to
Speaker 1: negative one hundred and ninety six degrees celsius. It's an
Speaker 1: extreme environment, yeah, And at that extreme low temperature, nitrogen
Speaker 1: gas condenses and coats the entire surface of the drug
Speaker 1: particle in a layer exactly one molecule thick.
Speaker 3: Yep.
Speaker 2: And because we know one single nitrogen molecule occupies precisely
Speaker 2: sixteen ankstrum squared, the machine just counts how much nitrogen
Speaker 2: was absorbed.
Speaker 1: And calculates the total microscopic surface area from there. That
Speaker 1: is wild.
Speaker 2: It's an incredibly elegant solution for measuring the unmeasurable. And
Speaker 2: if the scientists need a visual conformation of the morphology,
Speaker 2: they use a scanning electron microscope or SAM.
Speaker 1: But wait, the tech said, organic drug powders are terrible
Speaker 1: conductors of electricity, right.
Speaker 3: Yeah, they are.
Speaker 2: If you blast them with a high energy electron beam,
Speaker 2: they just burn up.
Speaker 1: So how do they get the picture?
Speaker 2: To solve this, the sample is placed in a vacuum
Speaker 2: chamber and they literally coat it in a microscopic atom
Speaker 2: thick layer of pure gold.
Speaker 1: Gold plating the medication, just to take a picture of it. Yes,
Speaker 1: that is insane. Now, all this meticulous data about surface
Speaker 1: area and solubility feeds directly into a mathematical model called
Speaker 1: the Noise Whitney equation.
Speaker 2: Right, the classic dissolution formula.
Speaker 1: Yeah, when you look at the formula and the text,
Speaker 1: it's just this giant string of variables. But conceptually it's
Speaker 1: really just describing the speed limit of dissolution exactly. It
Speaker 1: tells us that the rate a drug dissolves depends entirely
Speaker 1: on its surface area. The thickness of the stagnant fluid
Speaker 1: layer surrounding it, and the concentration gradient.
Speaker 2: Which basically means how much drug is already dissolved in
Speaker 2: the fluid versus how much is still solid.
Speaker 1: Right, and the output of that equation dictates a drug's
Speaker 1: fate in the Biopharmaceutical classification System, the BCS.
Speaker 2: Yes, the BCS categorizes drugs into four classes based on
Speaker 2: solubility and intestinal permeability.
Speaker 1: Okay, so classie is the best class Eiye, drugs are
Speaker 1: the golden standard.
Speaker 2: Yeah, high solubility, high permeability. They dissolve easily, just slip
Speaker 2: right into the bloodstream. And the word Class four drugs
Speaker 2: are the nightmare scenario for a formulation scientist. Low solubility
Speaker 2: and low permeability.
Speaker 1: Man, good luck making that work. Okay, So we have
Speaker 1: a perfectly characterized powder. The surface area is maximized, the
Speaker 1: crystal structure is locked in. How do we take that
Speaker 1: raw material and physically forge it into a pill a
Speaker 1: patient can actually swallow.
Speaker 2: Well, you can't just compress pure active ingredient. It we
Speaker 2: just crumble into dust.
Speaker 1: Right, You need excipients.
Speaker 2: Eccipients are the unsung heroes of pharmaceutics. You need diluents
Speaker 2: to add physical bulk, otherwise the pole would be the
Speaker 2: size of a grain of sand. Good point. You need
Speaker 2: binders to act as a glue under pressure, and disintegrants,
Speaker 2: which are designed to rapidly swell and literally explode the
Speaker 2: tablet apart once it hits the stomach.
Speaker 3: Acid.
Speaker 1: The text highlighted microcrystalline cellulose, known commercially as avisol.
Speaker 2: Right, Yes, avesol is heavily utilized because it's a dual threat.
Speaker 2: It's a fantastic dry binder, but it also draws water
Speaker 2: into the tablet via capillary action, acting a powerful disintegrin
Speaker 2: at the same time.
Speaker 1: That's super efficient. But combining chemicals is always a risk.
Speaker 1: Like the sources highlight this specific danger. If your active
Speaker 1: drug contains acamine groups, which are nitrogen based compounds, you
Speaker 1: have to avoid using the common deluent lactose.
Speaker 3: Oh yes, you really have to avoid that combination.
Speaker 1: Right, because if you mix a chemines and lactose, you
Speaker 1: trigger a major type condensation reaction.
Speaker 2: Which is wild because the Maillard reaction is the exact
Speaker 2: same chemical process that occurs when you see a steak
Speaker 2: on a grill. Wait, really yeah, Or like when you
Speaker 2: bake bread until the crest turns brown. It is a
Speaker 2: reaction between amino acids and reducing sugars.
Speaker 1: Okay, So in a kitchen that's delicious, sure, But.
Speaker 2: In a pharmaceutical bottle it means your highly engineered medication
Speaker 2: is browning, degrading, and completely losing its medical efficacy before
Speaker 2: the patient even opens the cap.
Speaker 1: Yikes. So, even if the chemistry is perfectly stable, the
Speaker 1: mechanical violence of a tablet press can still just ruin
Speaker 1: the batch right absolutely.
Speaker 2: These machines use immense hydraulic pressure to smash powder between
Speaker 2: two metal punches, and.
Speaker 1: If the formulation traps air or if the powder doesn't
Speaker 1: bind correctly, you get physical defects like capping.
Speaker 3: Right.
Speaker 2: Capping is where the top or bottom crown of the
Speaker 2: tablet just cleanly snaps off. This often happens because they
Speaker 2: use deeply concave punches that unfortunately trap air during the compression.
Speaker 1: And then there's lamination, which sounds like flooring, but here
Speaker 1: it's where the entile tablet splits horizontally into a stack
Speaker 1: of thin layers like a pastry.
Speaker 3: Yeah.
Speaker 2: Manufacturers also have to battle picking and sticking, where the
Speaker 2: powder physically adheres to the punch tips or the.
Speaker 1: Dye walls, just gumming up the machine exactly.
Speaker 2: This is usually due to excessive moisture or maybe insufficient
Speaker 2: lubrication in the powder.
Speaker 1: Plant, So how do they fix it?
Speaker 2: To mitigate this physically? The steel tooling is often plated
Speaker 2: with hard chromium or colloidal silica to really reduce that friction.
Speaker 1: Okay, And of course there is modeling, which I read
Speaker 1: isn't a structural failure but a cosmetic.
Speaker 2: One, right, an unequal ugly distribution of die that just
Speaker 2: makes the tablet look spoiled.
Speaker 1: Nobody wants to take a weirdly spody pill.
Speaker 3: Definitely not.
Speaker 1: So let's assume the tablet survives the press and it
Speaker 1: looks perfect. The final hurdle in manufacturing is controlling its destruction, right.
Speaker 1: The disintegration time is strictly enforced.
Speaker 3: Very strictly.
Speaker 2: A dispersable tablet which is meant to dissolve in a
Speaker 2: glass of water, has a hard limit of three minutes. Okay,
Speaker 2: A standard uncoded tablet gets fifteen minutes, film coded gets
Speaker 2: thirty minutes, and sugar coated gets up to an hour.
Speaker 1: But ento coded tablets have a radically different mission entirely.
Speaker 2: Oh completely, Because the stomach is essentially a vat of
Speaker 2: highly corrosive hydrochloric acid, some drugs are instantly destroyed by
Speaker 2: that acid, or they severely irritate the stomach lining, So
Speaker 2: entero coatings are designed to be impenetrable in acidic environments. Impenetrable, yes,
Speaker 2: The regulatory standard dictates an enteroic tablet must sit in
Speaker 2: acid for a full two hours without showing any signs
Speaker 2: of breaking apart. But the moment it passes into the intestines,
Speaker 2: which have a basic alkaline pH, it must completely dissolve
Speaker 2: within one hour.
Speaker 1: To pull off that kind of time release magic, they
Speaker 1: use pH sensitive polymers, right, materials like cellulose acetate FELLT
Speaker 1: or cap and various udroget polymers.
Speaker 2: Exactly, they remain tightly coiled and solid at a low pH,
Speaker 2: but they ionize and just dissolve at a high pH.
Speaker 1: It's essentially a chemical trip wire.
Speaker 3: That's a perfect way to describe it.
Speaker 1: But what'll really caught my attention in the reading was
Speaker 1: the traditional sugar coating process. The outline describes a four
Speaker 1: step process that literally sounds more like making gourmet candy
Speaker 1: than making a medicine.
Speaker 2: Yeah, which is why sugarcoating is largely being replaced by
Speaker 2: modern film coating.
Speaker 3: Now.
Speaker 2: It's just so incredibly time consuming, a labor intensive.
Speaker 1: Tell me about it. Step one is the seal coating.
Speaker 3: Right, yep.
Speaker 2: You have to waterproof the core tablet, often using a
Speaker 2: corn protein called zine, so the subsequent liquid syrups don't
Speaker 2: soak in and ruin the drug.
Speaker 1: And then step two is subcoding. Here, heavy sticky binders
Speaker 1: like gelatin or acacia are applied along with a dusting
Speaker 1: powder to round off the sharp mechanical edges of the.
Speaker 2: Tablet, and that step alone can increase the tablet's weight
Speaker 2: by up to one hundred percent.
Speaker 1: Wait, so making a sugar coated pill is basically a
Speaker 1: four step culinary process.
Speaker 2: It really is, because then step three brings the actual
Speaker 2: sugar syrup and the color dye to make it smooth.
Speaker 1: And finally, step four is polishing the dry tablet with
Speaker 1: carnabo wax in a rotating canvas drum to give it
Speaker 1: that elegant, glossy finish.
Speaker 2: It's an ordeal. If a manufacturer wants to skip that
Speaker 2: entire headache, they just use a capsule much easier. Hard
Speaker 2: gelatin capsules are brilliant in their simplicity, but the gelatin
Speaker 2: itself must be rigorously tested for its bloom strength. Bloom
Speaker 2: strength yeah, which typically needs to fall between one hundred
Speaker 2: and fifty and two hundred and fifty grams. The bloom
Speaker 2: test uses a standardized plunger to press into a chilled
Speaker 2: gelatin gel to measure its cohesive cross linking strength.
Speaker 1: Basically testing how squishy or tough it is.
Speaker 2: Basically, if the bloom strength is too low, the capsule
Speaker 2: is brittle and will shatter during shipping. But if it's
Speaker 2: too high, the gelatin is too tough and might not
Speaker 2: dissolve properly in the gastrointestinal tract.
Speaker 1: And the size and convention for these capsules is famously counterintuitive.
Speaker 1: You might assume a higher number means a bigger capsule,
Speaker 1: but they range from size zero zero down to size five.
Speaker 1: Size zero zero is the absolute massive horsepill size, while
Speaker 1: size five is the tiniest shell available.
Speaker 3: Yeah, you have to memorize that backwards.
Speaker 2: So okay, we have successfully manufactured a stable, perfectly characterized
Speaker 2: dosage form.
Speaker 1: The patient places it on their tongue and swallows right.
Speaker 2: And this is where we cross the border from pharmaceutics,
Speaker 2: which is making the drug, into pharmacokinetics.
Speaker 1: Which is the study of what the human body does
Speaker 1: to the drug. Here's where it gets really interesting, it.
Speaker 2: Really does, because the first barrier is absorption. How does
Speaker 2: the drug physically cross from the stomach into the bloodstream.
Speaker 1: Well, this entire processes governed by the Henderson Hasselback equation right,
Speaker 1: which looks at the pH of the digestive tract and
Speaker 1: the PKI or acid dissociation constant of the drug itself.
Speaker 2: If you connect this to the bigger picture understanding pH
Speaker 2: and PKI actually allows pharmacologists to weaponize the body's natural
Speaker 2: absorption systems. Well. Cell membranes are made of lipids, basically fats.
Speaker 2: For a drug to easily slip through a fat based membrane,
Speaker 2: it needs to be uncharged or unionized AH like dissolves
Speaker 2: like precisely, let's look at aspirin, which is a weak
Speaker 2: acid with a low PK of about three point five.
Speaker 2: When you drop ansperin into the highly acidic stomach, which
Speaker 2: has a pH of around one point five, the aspirin
Speaker 2: remains largely unionized. It carries no electrical charge.
Speaker 1: And because it's uncharged, it is highly.
Speaker 2: Livid soluble and absorbs rapidly right through the stomach wall.
Speaker 1: Wow. Conversely, consider a basic drug like atropine with a
Speaker 1: high PK of ten in stomach acid. Atropine becomes heavily ionized,
Speaker 1: It gains a strong a lay electrical charge, and charged
Speaker 1: molecules repel lipid membranes exactly.
Speaker 2: So the atropine bounces off the stomach wall and simply
Speaker 2: travels downstream until it reaches the alkaline environment of the intestines,
Speaker 2: where it finally loses its charge and absorbs.
Speaker 1: You know, you can bypass all of that gastric math
Speaker 1: by just using different routes of administration right.
Speaker 2: Oh, sure, Intravenous or IV administration gives one hundred percent
Speaker 2: bioavailability because you are injecting the active ingredient directly into
Speaker 2: the blood plasma.
Speaker 1: But the sources also point out the rectal route, highlighting
Speaker 1: a specific acronym pedia Pedia. Yes, THATP stands for peraldehyde
Speaker 1: or gotamine, diazepam, indomethicin, and aminophyleine. But why give a
Speaker 1: drug like diazepam rectally instead of just swallowing a pill?
Speaker 2: Well, Diazepam is often used to stop severe seizures. A
Speaker 2: seizing patient physically cannot swallow a tablet, and trying to
Speaker 2: find a vein for an IV and a convulsing patient
Speaker 2: is incredibly difficult.
Speaker 1: That makes total sense.
Speaker 2: Plus u Kosa is highly vascularized, meaning the drug absorbs
Speaker 2: rapidly into the blood, and more importantly, the lower rectum
Speaker 2: actually bypasses the liver's first pass metabolism.
Speaker 1: Oh or the liver chemically filters and destroys a large
Speaker 1: portion of an oral drug before it ever reaches systemic
Speaker 1: circulation exactly.
Speaker 3: You skip the liver entirely.
Speaker 1: Okay, here's another thing from the text. Sometimes the drug
Speaker 1: use swallow isn't actually a drug at all.
Speaker 3: Pro drugs co drugs are fascinating.
Speaker 1: I love this concept. A pro drug is like a
Speaker 1: biological trojan horse. It is an inactive, totally harmless chemical
Speaker 1: that is specifically designed to slip past the body's early
Speaker 1: defenses and distribution barriers.
Speaker 2: And then once it reaches the target, the body's own
Speaker 2: metabolic enzymes metabolize it, breaking it open to release the
Speaker 2: active drug inside.
Speaker 1: Lev Doopa is a prime example of this.
Speaker 2: Isn't it It is dopamine cannot cross the blood brain
Speaker 2: barrier to treat Parkinson's disease. The brain security system just
Speaker 2: blocks it outright.
Speaker 1: So we administer leve dopa instead, which is a pro
Speaker 1: drug structure that the brain readily imports.
Speaker 2: Right inside the brain tissue enzymes converted into active dopamine.
Speaker 2: Another one is innenelapl which is totally inactive until the
Speaker 2: liver metabolizes it into enoloprolate, which is a really potent
Speaker 2: blood pressure medication.
Speaker 1: And then there is also this bizarre category called hit
Speaker 1: and run drugs. The outline gives us the acronym gone
Speaker 1: rome to remember them, gone rome, yep, quanefidine, resser pain, omeprazol,
Speaker 1: and MAO inhibitors. From what I understand, the drug enters
Speaker 1: the body, does its job and is completely excreted. The
Speaker 1: drug is completely gone from the blood, but its biological
Speaker 1: effect persists for days. How is that even possible?
Speaker 2: It comes down to the type of chemical bond that
Speaker 2: drug forms. Take Omeprazol the acid reflux medication, Okay, it
Speaker 2: doesn't just block the proton pumps in your stomach lining
Speaker 2: it forms a permanent, irreversible covalent bond with them. The
Speaker 2: pump is basically fundamentally broken. Wow, So inin a few hours,
Speaker 2: your kidneys have filtered all the omeprozol out of your system.
Speaker 2: The drug is run away, but your stomach acid remains
Speaker 2: low for days because your body has to literally synthesize
Speaker 2: entirely new proton pumps from scratch to replace the destroyed ones.
Speaker 1: That is wild, and to control those concentrations, doctors utilize
Speaker 1: two dosing strategies. A loading dose, which is a massive
Speaker 1: initial hit designed to rapidly fill the body's volume of
Speaker 1: distribution and get the drug concentration up to the therapeutic
Speaker 1: threshold immediately.
Speaker 2: And once you're there, you switch to a much smaller
Speaker 2: maintenance does.
Speaker 1: Which is carefully calculated to perfectly match the rate at
Speaker 1: which your liver and kidneys are clearing.
Speaker 2: The drug exactly so once the drug reaches its target tissue,
Speaker 2: we move into pharmacode dynamics. We know what the body
Speaker 2: does to the drug, now we examine what the drug
Speaker 2: does to the cells. Right, the body operates via receptors,
Speaker 2: which are protein structures on the surface of cells that
Speaker 2: basically act as biological.
Speaker 1: Locks, and the drug molecule is the key. But pharmacology
Speaker 1: breaks that key down into two specific properties, right, Yes,
Speaker 1: First is affinity, which is simply the drugs ability to
Speaker 1: find the lock and insert itself into the keyhole. And
Speaker 1: second is intrinsic activity or efficacy. This is the drug's
Speaker 1: ability to actually turn the lock, open the door and
Speaker 1: trigger a cellular response.
Speaker 3: Spot on.
Speaker 2: So if a drug has both affinity and efficacy, we
Speaker 2: call it an agonist. It binds and activates. Okay, But
Speaker 2: an antagonist is a drug that has affinity but zero efficacy.
Speaker 2: It jams itself into the lock perfectly, but it cannot turn.
Speaker 1: And furthermore, because it's stuck in the keyhole, it blocks
Speaker 1: the body's natural chemicals from binding. The text divides this
Speaker 1: into competitive and non competitive antagonism. Let me try an
Speaker 1: analogy here. Competitive antagonism is like a massive game of
Speaker 1: molecular musical chairs.
Speaker 3: Okay, I'm tracking the.
Speaker 1: Drug and the body's natural chemical are fighting for the
Speaker 1: exact same seat on the receptor. If you flood the
Speaker 1: system with enough natural chemical you can basically outcompete the
Speaker 1: drug and win the seat back.
Speaker 3: That's right.
Speaker 1: But non competitive antagonism is that like someone coming into
Speaker 1: the room and just stealing the chair entirely.
Speaker 2: That is an incredibly accurate way to visualize it. In
Speaker 2: non competitive antagonism, the drug doesn't bind to the main keyhole.
Speaker 2: It binds to an allosteric site, a completely different area
Speaker 2: on the receptor entirely, and when it binds there, it
Speaker 2: physically warps and distorts the shape of.
Speaker 3: The main keyhole.
Speaker 2: Now, it doesn't matter how much natural chemical you pump
Speaker 2: into the system, the original keyhole basically doesn't exist anymore.
Speaker 1: So in mathematical terms, this physically lowers the maximum possible
Speaker 1: effect or VMAX of the tissue.
Speaker 2: Yes, we just discussed a member zole permanently shutting down
Speaker 2: the H plus k plus atpayse pump. Another example is digoxin,
Speaker 2: which non competitively inhibits K plus atpays pump in heart
Speaker 2: muscle to regulate heart failure.
Speaker 1: Right now, when you have multiple drugs in the system,
Speaker 1: you get combined effects like physical interactions, which involve something
Speaker 1: like administering activated charcoal during an overdose.
Speaker 2: Yeah, the charcoal doesn't alter cellular receptors. It physically absorbs
Speaker 2: alkali poisons in the stomach like a bunge, so they
Speaker 2: just can't end of the blood.
Speaker 1: Then chemical interactions occur when drugs react with each other
Speaker 1: in the plasma, like if a patient is poisoned by cyanide,
Speaker 1: doctors administer nitrates.
Speaker 2: The nitrates chemically alter the iron in your blood to
Speaker 2: form methemoglobin, which actively hunts down and binds the deadly
Speaker 2: cyanide radical amazing.
Speaker 1: And then you have physiological interactions where two different drugs
Speaker 1: bind to two completely separate receptors, but they produce opposite
Speaker 1: physical outcomes, like.
Speaker 2: Histamine, which acts on H one receptors to severely drop
Speaker 2: your blood pressure during an allergic reaction.
Speaker 1: Right, but adrenaline acts on adrenergic receptors to radically raise
Speaker 1: your blood pressure.
Speaker 2: They don't interact chemically, but physiologically they just cancel each
Speaker 2: other out. This is why understanding precise chemical antidotes is
Speaker 2: a literal matter of life and death.
Speaker 1: The text lists specific reversals that every pharmacist needs on standby,
Speaker 1: like if a patient overdoses on benzodiazepins, you administer plume
Speaker 1: en l, which aggressively competes for the receptor.
Speaker 2: If they are exposed to toxic carbon pesticides, you give
Speaker 2: atropine to block the overstimulated nervous.
Speaker 1: System, and conversely, If a patient is poisoned by the
Speaker 1: belladonna plant, which contains legal amounts of natural atropine, you
Speaker 1: administer the anadote physostigmine.
Speaker 2: It's a high stakes chemical chess match, and we must
Speaker 2: also account for tolerance, right. Natural tolerance is genetic. Rabbits,
Speaker 2: for instance, have natural enzymes that rapidly destroy atropine, meaning
Speaker 2: they can eat toxic belladonna leaves without showing any symptoms.
Speaker 1: Healthy rabbits very but acquired.
Speaker 2: Tolerance happens when a human body down regulates its receptors
Speaker 2: in response to constant drug exposure, like a patient eventually
Speaker 2: requiring higher doses of the antipsychotic chlor promisine just to
Speaker 2: achieve the same sedative effect.
Speaker 1: Okay, so we have formulated the perfect crystal, pressed it
Speaker 1: into a flawless tablet, mapped its absorption via pH, and
Speaker 1: tracked its antagonistic action on cellular receptors. But none of
Speaker 1: these matters, and none of it is legal without Segment
Speaker 1: five quality control. Oh yes, the pharmaceutical industry doesn't just
Speaker 1: operate on trust. The analysis lab is the final absolute
Speaker 1: safety net. You have to scientifically prove that the microscopic
Speaker 1: white powder in the bottle is purely what you claim
Speaker 1: it is, and we prove.
Speaker 2: It using spectroscopy. Spectroscopy is the study of how electromagnetic
Speaker 2: radiation so light, radio waves, magnetic fields, interacts with matter.
Speaker 2: Every single molecule absorbs and emits energy in a completely
Speaker 2: unique mathematical fingerprint.
Speaker 1: Let's break down the specific machines used to find those fingerprints.
Speaker 1: First is NMR nuclear magnetic resonance. When I read about this,
Speaker 1: it sounded exactly like an MRI machine used in hospitals,
Speaker 1: but like scaled down for molecules.
Speaker 2: Because it operates on the exact same quantum principles.
Speaker 1: Yeah.
Speaker 2: By applying a powerful external magnetic field and hitting the
Speaker 2: drug sample with specific radio frequencies, NMR actually forces the
Speaker 2: nuclei of the atoms to flip their magnetic spin. Wow. Yeah,
Speaker 2: And by measuring the energy release when they flip back,
Speaker 2: chemists can map the exams carbon and hydrogen framework of
Speaker 2: the drug.
Speaker 1: Then there is mass spectrometry. Now this sounds incredibly violent.
Speaker 1: The outline specifically mentions using a quadrupole or a time
Speaker 1: of flight analyzer. Instead of gently measuring magnetic spin, a
Speaker 1: mass spectrometer blasts the drug molecule with high energy electrons,
Speaker 1: literally shattering it into pieces.
Speaker 3: It is destructive.
Speaker 2: Yes, a quadruple mass spectrometer uses four parallel magnetic rods.
Speaker 2: As the shattered molecular fragments fly through the rods, the
Speaker 2: fluctuate electrical fields filter them based on their exact mass
Speaker 2: to charge ratio.
Speaker 1: It's like sorting coins by precisely weighing them as they
Speaker 1: fly through the air.
Speaker 3: That's a fun way to put it. Yeah.
Speaker 2: For detecting unpaired electrons, which are highly reactive free radicals,
Speaker 2: chemists use electron spin resonance or ESR, and.
Speaker 1: The text notes they calibrate the liquid sample machines using
Speaker 1: a standard chemical called DPPH.
Speaker 2: Right. Yes, DPPH is a famously stable free radical, so
Speaker 2: it provides a perfect reliable baseline signal for the machine
Speaker 2: before you u even test your unknown drug.
Speaker 1: And when we need to detect specific inorganic metal ions,
Speaker 1: say ensuring there is exactly the right amount of sodium,
Speaker 1: potassium or lithium in a formulation, we turn to flame photometry.
Speaker 2: It is based on the simple principle that different metals
Speaker 2: basically burn in different.
Speaker 1: Colors, right like fireworks.
Speaker 2: Exactly by asp reading the drug into a hot flame,
Speaker 2: and measuring the exact wavelength of the emitted light, we
Speaker 2: can quantify the.
Speaker 1: Metals and similarly, atomic absorption spectroscopy or AAS uses a
Speaker 1: specific hollow cathode lamp. Instead of measuring the light the
Speaker 1: metal emits, it measures the specific wavelengths of light the
Speaker 1: metal ions absorbed from the lamp yep.
Speaker 2: And finally, there's turbodymmetry. Unlike the others, this isn't looking
Speaker 2: for molecular fingerprints at all. It measures the loss of
Speaker 2: intensity of transmitted light caused by solid particles suspended in a.
Speaker 1: Liquid, essentially how cloudy is the water pretty much.
Speaker 2: The text specifically notes this is vital for determining the
Speaker 2: growth of bacteria in culture media.
Speaker 1: So if you shoot a LA LA through a liquid
Speaker 1: drug sample and the light scatters because the liquid has
Speaker 1: turned cloudy, it means bacteria are rapidly.
Speaker 2: Multiplying the batch is contaminated. Without these spectral and analytical technologies,
Speaker 2: modern medicine would just regress to the dangerous, unregulated guesswork
Speaker 2: of the nineteenth century.
Speaker 1: So what does this all mean.
Speaker 2: Well, they guarantee that the crystalline polymorph, the dissolution rate,
Speaker 2: and the exact milligram dasage are perfectly consistent in a
Speaker 2: factory producing ten million pills a day.
Speaker 1: Incredible. Well, we have covered an astronomical amount of ground today,
Speaker 1: tracking the journey of a medicine from raw bulk powder,
Speaker 1: through the brutal pressures of manufacturing, into the acidic battleground
Speaker 1: of the stomach, all way to a protein receptor on
Speaker 1: a single cell.
Speaker 3: It's a long journey.
Speaker 1: And because we promised a masterclass experience for our learners,
Speaker 1: it is time for a quick review exercise to lock
Speaker 1: in your retention. Listener, see if you can answer these
Speaker 1: two rapid fire questions before my expert colleague does. Question one,
Speaker 1: in manufacturing, which hard gelatin capsule size is physically larger
Speaker 1: A size zero zero or a size five? In question two,
Speaker 1: what is the acronym for the primary drugs given by
Speaker 1: the rectal route?
Speaker 3: Take a second right, Well.
Speaker 2: For question one, remember it's the counterintuitive sizing size thou
Speaker 2: zero zeros is the massive largest capsule. Well, size five
Speaker 2: is the absolute smallest. Perfect, And for question two, the
Speaker 2: acronym for rectal administration is PDA per aldehyde or gotamine,
Speaker 2: diazepam into methicine and amenophiline. Absolutely nailed it, And as
Speaker 2: we close, I want to leave you with the thought
Speaker 2: concerning the future. Oh please do We've spent this time
Speaker 2: dissecting the physics of pressing dry powder into solid tablets
Speaker 2: and navigating stomach acid. But the cutting edge of pharmacology
Speaker 2: is moving rapidly away from simple chemical molecules. We are
Speaker 2: entering the era of biopharmaceuticals, massive, incredibly fragile biological structures
Speaker 2: like mRNA therapies and monoclonal antibodies.
Speaker 1: Right, which are so sensitive Exactly.
Speaker 2: These biologicals cannot survive the sheer four of a tablet press,
Speaker 2: and they would instantly degrade in stomach acid. As these
Speaker 2: therapies become the norm, how will our traditional century old
Speaker 2: methods of oral delivery and excipient engineering have to evolve?
Speaker 1: Wow, that's a huge question. The tiny white pill as
Speaker 1: we know it might soon become a relic of the
Speaker 1: past entirely. Well, thank you for joining us on this
Speaker 1: deep dive. Keep learning, keep questioning your textbooks, and keep
Speaker 1: exploring your sources. And the next time you hold a
Speaker 1: simple headache tablet in the palm of your hand, remember
Speaker 1: the invisible complexity inside it. Catch you next time