Metformin
Presented By: Sghayra Ahmed Alshebli
ID: M00009043
PHB100 Chemistry
metformin hydrochloride structural formula
biguanide • hydrophilic • basic
Metformin
Presented By: Sghayra Ahmed Alshebli
ID: M00009043
PHB100 Chemistry
metformin hydrochloride structural formula
biguanide • hydrophilic • basic
1. Drug introduction & therapeutic relevance
Generic name, drug class, therapeutic use, and why the chemistry matters
RUBRIC ITEM 1
Metformin at a glance
• Generic name: metformin; marketed drug form is commonly metformin hydrochloride.
• Drug class: biguanide antihyperglycemic agent.
• Therapeutic use: adjunct to diet and exercise to improve glycemic control in type 2 diabetes mellitus.
• Key chemistry idea: many nitrogen atoms make the drug basic, polar, and water-soluble.
↓ hepatic
glucose output
↓ intestinal
glucose absorption
↑ peripheral
insulin sensitivity
Pharmacologic effect reported in prescribing information
Main idea for the presentation
Metformin is small, but the nitrogen-rich biguanide core controls its acid–base behavior, water solubility, hydrogen bonding, and formulation choices.
Sources: DailyMed metformin tablet label; DailyMed RIOMET label.
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2. Dosage form examples: metformin is an oral drug
Available examples include immediate-release tablets, extended-release tablets, and oral solution/suspension
PICTURE EXAMPLES
Immediate-release tablet label: 500 mg
Extended-release tablet label: 500 mg ER
Oral solution label: 500 mg/5 mL
Examples:
• IR tablets: common strengths include 500, 850, and 1000 mg.
• ER tablets: designed for slower release; strengths vary by product.
• Oral solution/suspension: useful when swallowing tablets is difficult.
Not typically formulated as injection, inhaler, eye drop, or topical cream
Images and dosage examples: DailyMed/NLM label images.
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3. Chemical structure: a nitrogen-rich biguanide salt
Metformin hydrochloride is the form usually named on dosage-form labels
RUBRIC ITEM 2
Official structural formula shown in the DailyMed RIOMET label
Free base
Molecular formula: C₄H₁₁N₅
Molar mass: 129.16 g/mol
Canonical SMILES: CN(C(=N)N=C(N)N)C
Hydrochloride salt
Formula: C₄H₁₁N₅·HCl = C₄H₁₂ClN₅
Molar mass: 165.62–165.63 g/mol
This is the salt used in tablets and oral solution.
High nitrogen count = high polarity and basicity
Sources: DailyMed RIOMET label; DailyMed tablet label; PubChem CID 4091; IUPHAR/BPS Guide to Pharmacology.
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4. Bonding and Lewis-structure spotlight
Identify bond types and explain an important C=N amidine/biguanide part
RUBRIC ITEM 2
Bonds visible in the structure: C–N, C=N, N–H, C–H; salt pair with Cl⁻
Main bond types
• C–N single σ bonds: connect the biguanide chain and dimethyl group.
• C=N double bonds: one σ bond + one π bond; electron density is delocalized.
• N–H and C–H covalent bonds; metformin HCl exists as an ionic salt with Cl⁻.
Lewis spotlight: amidine segment
:N–C(=NH)–N:
“:” represents a nitrogen lone pair in this simplified Lewis view.
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The carbon has three electron regions, so it is trigonal planar and sp².
2
Nitrogen atoms carry lone pairs; the imine N participates in the C=N π bond.
3
After protonation, positive charge is resonance-stabilized over the biguanide nitrogens.
Lewis structure takeaway: many N lone pairs → proton accepting + H bonding
Sources for structure and physicochemical data: DailyMed RIOMET label; IUPHAR/BPS; PubChem.
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5. Hybridization: sp² biguanide carbons + sp³ methyl carbons
Metformin has no aromatic ring; the key geometry comes from C=N and methyl groups
RUBRIC ITEM 2
Two C=N carbon centers are sp²; two CH₃ carbon atoms are sp³.
Selected Atoms
Atom selected
Hybridization
Reason
C of C=N in biguanide
sp²
Three electron regions; σ + π bond; planar resonance
Methyl C in –N(CH₃)₂
sp³
Four σ bonds around carbon; tetrahedral
Aromatic/alkene C?
None
Metformin has no benzene ring and no C=C alkene
sp² ≈ 120°
sp³ ≈ 109.5°
Sources: DailyMed structure; PubChem and IUPHAR/BPS structural identifiers. Hybridization based on standard valence-bond theory.
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6. Functional groups: biguanide chemistry drives drug behavior
Functional groups explain solubility, basicity, and hydrogen bonding
RUBRIC ITEM 3
Metformin functional-group map
The major functional group is a substituted biguanide with imine/amidine and amino nitrogens.
Biguanide core
Strongly basic; protonation gives a stable cation; increases water solubility.
Imine / amidine C=N
Adds polarity, resonance, and an sp² carbon center; supports hydrogen bonding.
Amino / imino N–H
Hydrogen-bond donors; helps form strong interactions with water.
Dimethylamino part
Small hydrophobic contribution,but still attached to a polar/basic nitrogen.
No carboxylic acid, phenol, ester, alcohol, aromatic ring, or carbonyl group
Sources: DailyMed structure; PubChem and IUPHAR/BPS identifiers/physicochemical data.
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7. Polarity, hydrogen bonding & intermolecular forces
A polar cationic drug makes strong interactions with water
RUBRIC ITEM 2–3
metformin-H⁺ / Cl⁻
H₂O
ion–dipole attractions
N–H···O
hydrogen-bond donation
:N···H–O
hydrogen-bond acceptance
dispersion
small but present
Measured/computed polarity clues
H-bond acceptors: 5 • donors: 3
TPSA: 91.49 Ų • XLogP: −0.54
Sources: IUPHAR/BPS Guide to Pharmacology for H-bond counts, TPSA, XLogP; DailyMed for salt/structure.
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8. Molecular formula, molar mass & mass percentage
Calculation shown for the hydrochloride salt used in dosage forms
RUBRIC ITEM 4
Salt formula selected for calculation
Metformin hydrochloride = C₄H₁₁N₅·HCl = C₄H₁₂ClN₅
Atomic weights used: C 12.011, H 1.008, N 14.007, Cl 35.45
Molar mass calculation
Element
Atoms
Atomic mass
Contribution
C
4
12.011
48.044
H
12
1.008
12.096
N
5
14.007
70.035
Cl
1
35.45
35.450
Total
165.625 g/mol
Mass percentage
Element
Mass %
Carbon
48.044 ÷ 165.625 × 100 = 29.01%
Nitrogen
70.035 ÷ 165.625 × 100 = 42.29%
Hydrogen
12.096 ÷ 165.625 × 100 = 7.30%
Chlorine
35.450 ÷ 165.625 × 100 = 21.40%
Required: at least two elements → shown here for C, N, H, and Cl
Formula and molar mass values from DailyMed labels and PubChem; calculations shown using standard atomic weights.
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9. Solubility & pharmaceutical formulation
High water solubility supports oral solution and rapidly dissolving oral products
RUBRIC ITEM 5
Picture examples: oral solution and tablet products
Water solubility
DailyMed reports metformin HCl is freely soluble in water and 2.0 g dissolves in 20 mL water (~100 mg/mL).
Formulation effect
Because it is highly soluble, tablets can dissolve readily and oral solution at 500 mg/5 mL is practical.
Biopharmaceutics
Metformin HCl is described as BCS Class III: high solubility but lower permeability, so absorption is not limited by dissolution only.
ER dosage forms slow release; solubility still supports dissolution once released
Sources: DailyMed tablet and RIOMET labels for solubility/dosage forms; Metry et al. (2021) for BCS Class III.
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10. Equilibrium, ionization & pH effect
Metformin is basic and remains highly protonated at physiological pH
RUBRIC ITEM 6
Acid/base classification
Metformin is basic, not acidic and not amphoteric. It has proton-accepting nitrogen atoms and no acidic group such as –COOH.
Ionization equilibrium
B + H⁺ ⇌ BH⁺
Label pKa = 12.4; pH of a 1% aqueous HCl salt solution ≈ 6.68
stomach ~1.5
blood 7.4
pKa 12.4
pH 0
pH 14
Using fraction protonated = 1 / (1 + 10^(pH − pKa))
pH
Fraction protonated
1.5
~100%
6.8
>99.999%
7.4
~99.999%
12.4
50%
Practical effect: high solubility; limited passive membrane diffusion; transporter-mediated absorption/excretion matters
Sources: DailyMed labels for pKa and pH; Metry et al. (2021) for permeability/transport relevance.
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11. Pharmacy relevance
Chemistry helps pharmacists interpret formulation, dosing, counseling, and safety
RUBRIC ITEM 7
Chemistry
basic salt
hydrophilic
ionized
Formulation
IR tablet
ER tablet
oral solution
Patient use
take with meals
ER: swallow whole
Safety
renal function
lactic acidosis risk
1. Salt and dose interpretation
Labels usually state metformin hydrochloride; the RIOMET label gives 500 mg HCl ≈ 389.93 mg metformin base per 5 mL.
2. Formulation counseling
High solubility supports oral solution. Extended-release products should not be crushed, cut, or chewed when the label says swallow whole.
3. Monitoring and interactions
Because metformin is hydrophilic/cationic and renally cleared, renal function and interacting drugs matter clinically.
Chemistry → formulation → safe use: this is the pharmacist’s connection
Sources: DailyMed RIOMET and tablet labels; Metry et al. (2021).
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13. References (APA format)
Reliable sources used for structure, dosage forms, solubility, pKa, and therapeutic use
RUBRIC ITEM 8–9
Image sources: DailyMed label images for metformin HCl structure, tablet labels, and RIOMET oral solution labels.
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PubChem. (n.d.). Metformin. PubChem. https://pubchem.ncbi.nlm.nih.gov/compound/Metformin
DailyMed - RIOMET- metformin hydrochloride solution. (n.d.). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=05d4df4b-dfe8-4828-b423-a3d4f2c4114a
DailyMed - METFORMIN HYDROCHLORIDE tablet, film coated METFORMIN HYDROCHORIDE- metformin tablet, film coated. (n.d.). https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=23aa0072-365c-4d13-9aa7-ae23f7e00ee4
Checking your browser - reCAPTCHA. (n.d.). https://pubmed.ncbi.nlm.nih.gov/33450218/