Antibiotic extraction principle: phase partitioning of penicillin at neutral pH During liquid–liquid extraction, where does penicillin predominantly remain at approximately neutral (“normal”) pH?

Introduction / Context:
Industrial recovery of penicillin relies on acid–base extraction. Penicillin is a weak acid: its ionization state, and thus solubility in water versus organic solvents, depends on pH. Recognizing the phase behavior guides efficient downstream processing.

Given Data / Assumptions:

• “Normal” pH is taken as approximately neutral (around pH 7).
• Penicillin has acidic functionality with pKa well below neutrality.
• Distribution depends on ionized (aqueous) vs. nonionized (organic-soluble) forms.

Concept / Approach:
Weak acids are predominantly deprotonated (ionized) at pH values above their pKa. Ionized species are more water-soluble and less soluble in nonpolar organic solvents. Therefore, at neutral pH, penicillin exists largely as its anionic form and partitions into the aqueous phase. For extraction into an organic solvent, the broth is acidified (pH ~2–3) to protonate penicillin, increasing its solubility in solvents such as amyl acetate or butyl acetate.

Step-by-Step Solution:

Verification / Alternative check:
Standard downstream protocols: acidify for solvent extraction (organic phase capture), basify to back-extract into water as the salt—corroborating the partition behavior.

Why Other Options Are Wrong:

• Solvent phase: typical only at acidic pH when penicillin is protonated.
• Equal partition/precipitation: not representative at neutral pH for typical systems.
• Ion-exchange resin: a different unit operation not implied by the question.

Common Pitfalls:
Forgetting that extraction direction reverses with pH adjustments; misidentifying “normal pH” as acidic.

Final Answer:
Aqueous phase