Buffered Solution Flashcards
What are buffers?
Define: Aqueous solutions containing compounds which help to resist pH changes after addition of small quantities of acid or base.
- *Acidic buffers:** weak acid HA & conjugate base A- (provided by its salt)
- *Basic buffers:** weak base B & conjugate acid BH+ (provided by its salt)
How does a buffer work?
Acid Buffer:
- H3O+ + A- HA + H2O
- When adding additional acid, A- takes up the H3O+ ions
- OH- + HA A- + H2O
- When adding additional base, HA takes up the extra OH- ions
Basic Buffer:
- BH+ + OH- B + H2O
- When adding additional base, BH+ takes up the extra OH- ions
- B + H3O+ BH+ + H2O
- When adding additional acid, B takes up the extra H3O+ ions
What is the henderson-hasselbalch equation?
WA buffer:
- pH = pKa + log([A-]/[HA])
- pH = pKa + log([salt]/[acid])
WB buffer:
- pH = pKa + log([B]/[HB+])
- pH = pKa + log([Base]/[salt])
“United” equation:
- pH = pKa + log([“Base”]/[“Acid”])
- ([“Conjugate Base”]/[“Conjugate Acid”])
What is the importance of ionic equilibria in pharmaceutical science
- Many drugs and ingredients are organic weak electrolytes.
- Weak electrolyte can exist in an ionized form and an unionized form
- The degree of ionization directly affects drug physicochemical properties, such as solubility, hydrophobicity, stability, etc.
- The degree of ionization directly affects drug dissolution, absorption, transportation, and excretion.
- Ionized forms are more water-soluble and less lipophilic
- Unionized forms are less water-soluble but more lipophilic, and more permeable to lipid membrane
- pH partition hypothesis for drug absorption: the absorption of a weak electrolyte is determined mainly by its existing unionized form at the site of absorption, when drug are absorbed from the GI tract by passive diffusion. (also see Martin’s Page 238)
What are the titration and Neutralization curves?
What are buffer capacities?
Buffer capacities (): the magnitude of the resistance to pH changes of a buffer.
It is the ratio of the increment of strong base or strong acid to the change in pH.
Define: = B/pH
- B: small increment of strong acid or base added to buffer in equivalent per liter (Eq/L)
- pH: pH change upon adding the strong acid or base
- : buffer capacity, usually ignore the unit
describe Buffer Capactiies?
Buffer capacities is the function of Ka, [H3O+], and total concentration C (= [A]+[B] )
Van Slyke’s Equation
The maximum buffer capacity max occurs when
[H3O+] = Ka, i.e. pH = pKa
max = 2.303 C (1/4)
max = 0.576 C
What are teh Pharmaceutical Buffer Systems and the requirements?
Requirements
- Buffer solutions are frequently used in the preparation of injections and ophthalmic dosage forms.
- The choice of suitable buffer depends on required pH and buffer capacity.
- The selected buffer must be compatible with other excipients
- Buffer must have low toxicity.
Most acceptable buffer systems are base on
- Carbonates
- Citrates
- Lactates
- Phosphates
- Borates are used for external applications only
What are some examples of buffers?
A combintion of A weak acid and its conjugate base
A weak base and it conjugate acid
- Acetic acid & Sodium acetate
- Boric acid & Sodium borate
- Citric acid & Sodium citrate
- Phosphoric acid & Potassium phosphate
- Carbonic acid & Sodium carbonate
- Ammonium hydroxide & Ammonium nitrate
What are useful buffer systems?
Components pH Range
HCL, Sodium Citrate 1-5
Citric acid, sodium citrate 2.5 – 5.6
Acetic acid, sodium acetate 3.7 – 5.6
K2HPO4, KH2PO4 5.8 – 8
Na2HPO4, NAH2PO4 6 – 7.5
Borax, Sodium Hydroxide 9.2 - 11
What are teh physiologic buffer systems?
Blood
- pH ~ 7.4 (7.35-7.45)
- Primary buffer systems in the plasma – carbonic acid/bicarbonate; phosphoric acids; plasma proteins;
- Secondary buffer systems in the erythrocytes – Hemoglobin/oxyhemoglobin;
- Na+ as the major cation (counter ion to balance)
- ~ = 0.0385 [HCO3-]/[H2CO3]
Lacrimal fluid (eye fluid, tears)
- pH ~ 7.4 (7 - 8)
- Buffer systems: Carbonic acid/bicarbonate; phosphoric acids; plasma proteins;
- Na+ as the major cation (counter ion to balance)
Urine:
- pH ~ 6.0 (4.5 -7.8)
- H+ retain and excretion by kidney to adjust the pH
What is the blood buffer system?
In blood plasma the carbonic acid and bicarbonate equilibrium buffers the pH in the range 7.35-7.45 (primary buffer)
Why do we use buffers in pharmacy?
Buffers are used to maintain the pH of drug solutions and/or to control the degree of the ionization of a drug
- Solubility
- Absorption
- Stability
- Tissue irritation
What is the influence of buffer capacity and pH on tissue irritation and safety?
Generally, tissue irritation is related to
- pH difference between the administered solution and the physiologic fluid
- Buffer capacity of the solution and the physiologic fluid – When pH is different from physiological pH, the Lower buffer capacity, therefore cause less discomfort
- Volume of the solution related to the physiologic fluid volume
Parental solutions: usually not buffered or with low buffer capacity, so that the buffers of blood may bring them back to the physiological pH
Ophthalmic solutions: boric acid
Others: nasal delivery, abraded surface
What is the formulation challenge?
Balance of pH and for tissue irritation and safety, therapeutic effects, drug solubility and stability.
