Buffered isotonic solutions

buffered isotonic solutions unit-5 in pp-1 jntuh syllabus r13,14,15 batches

2. Contents

e The Buffer Equation
« Buffer Capacity
« Buffers in
pharmaceutical and Biologic Systems
e Buffered Isotonic Solutions
e Methods of Adjusting Tonicity and pH

3. Buffered Solutions

° Combination of a weak acid and its conjugate base

HA + OH 2 A + HO

+ Combination of a weak base and its conjugate acid

A-+H30+ = HA + OH:

4. The Buffer Equation
+ A Weak Acid and Its Salt

HAc+HO = H,0*+Ac

Kı[HAc][H,0] = K2[H30*][Ac"]

MES
u (HAcb— acid

-log[H30+]= - logKa - log[acid] + log[salt]

5. The Buffer Equation

° A Weak Acid and Its Salt

Buffer equation or Henderso
Dissociation exponent

6. The Buffer Equation
+ A Weak Base and Its Salt

B+HO = OH+BH*+

k= OHI
base

7. Common ion effect

* when Sod. acetate is added to acetic acid...
_ [HO*][Ac]
4 [HA]

Ka

is momentarily disturbed since the acetate ion supplied by th

HAc + H,0 H,0*+ Ac

The ionization of HAc is repressed upon the addition of the q

8. The Buffer Equation

+ A weak base and its salt

[OH] = [base]

K [salt]

9. The Buffer Equation
+ A Weak Acid and Its Salt

* Buffers are not ordinarily prepared from weak bases

10. pH el Se F= 12

1. Altering the ionic strength
(D Addition of neutral salts
(2) Dilution (alter activity coefficients)

2. Temperature
The pH of the most basic buffer was found to cha

11. pH indicator

Acid indicator2] 42

Hin + HJO— H,O+ + In-

Acid color

K, = Hole
[Hin}—

12. PH indicator

[base]
. pH = pKin + log “sel tasar 7 1/10-10/1

* From experience, one cannot discern a change from the acid color to

* The effective range of the indicator is...

pH =pKin + 1

“base 10/11 1/10

13. Buffer capacity

e ...the magnitude of the resistance of a buffer to pH changes

buffer capacity
= büffer efficiency
=\buffer index

AB : small increment in gram equivalents/Liter of strong:

14. Buffer capacity (4}2] °]-2)

HAc + NaOH = NaAC +H;0
(0.1- 0.01) 0.01 (0.1+ 0.01)
e Before the addition a NaOH
salt]
Sr = 4.76
e After the addition of NaOH
[salt] + [base]

H=pKa + log “22
Pr = [acid] - [base] ua

pH=pKa + log

15. Buffer capacity
® A more exact equation for buffer capacity (1914, 1922)

Kas [H30+]
(Ka + [H30+])?

TB 20:

c : total buffer conc.(sum of the molar conc. of the aq

B ---- at any [H3O+]

16. Maximum Buffer capacity

* Bmax occurs where pH = pK ([H30*] = Ka)

42
[HOT _ 2.303, 0

B max = 2.303 °C “e [H¿0-77? = 4

B max = 0.576 + C
(

17. Characteristics of Buffer Capacity

...is not a fixed value, but rather depend on the amount
...depends on the value of the ratio [salt]/[acid] and ma
The greatest capacity(Bmax) occurs where [salt]/[acid]

Because of interionic effects, buffer capacities do not in

18. Universal Buffer

° Total buffer capacity of a universal buffer (combina

19. In Vivo biologic buffer systems

+ Blood
© Primary buffers : Plasma ;
NaHCO;-- H,CO;, NaHPO,--NaH,PO,, protein
@) Secondary buffers : Erythrocytes ; hemoglobin-oxyhemoglobin, K,Hp

+ Lacriminal fluid
- pH: 7.4 (range 7 — 8 or slightly higher)

+ Urine
- pH: 6.0 (range 4.5 — 7.8)
- below normal...hydrogen ions are excreted by the kidney.
- above pH 7.4...hydrogen ions are retained by action of the kidney.

20. Pharmaceutical buffers

e = ophthalmic soln.

¢ colormetric determination of pH

research studies in which pH must be

21. Pharmaceutical buffers

¢ Clark-Lubs mixtures and pH

(a) HCl & (KCI, pH 1.2 - 2.2

(b) HCI & potassium biphthalate, pH 2.2 - 4.0
(C) NaOH & potassium biphthalate,pH 4.2 - 5.8
(d) NaOH & KH,PO,, pH 5.8 - 8.0

(e) H3BO3, NaOH $ (KO, pH 8.0 - 10.0

22. Preparation of pharmaceutical buffer solutions

e Steps for development of a new buffer

(® Select a weak acid having a pKa approximately equal to the p
@ Calculate the ratio of salt & weak acid required to obtain the dq

@) Consider the individual conc. Of the buffer salt & acid needed

* Individual conc. : 0.05 ~ 0.5M
* buffer capacity : 0.01 ~ 0.1

23. Preparation of pharmaceutical buffer solutions

e Steps for development of a new buffer
(4) Availability of chemicals, sterility of the final soln, stability of

ex) borate buffer — toxic effect — not be used for oral or parenter.

6) Determine the pH and buffer capacity using a reliable pH mete}

24. Buffer in
pharmaceutical and biologic systems

» Influence of buffer capacity and pH on tissue irritati

* Tissue irritation will be minimal when...

(a) Buffer solution— 8 , Volume

(b) Physiologic fluid - Bf), Volume ff

25. Buffer in
pharmaceutical and biologic systems

+ Stability vs. optium therapeutic response

* Undissociated form of a weakly acidic or basic drug has a higH

* Molecular form is lipid soluble & can penetrate body membra

26. Buffer in
pharmaceutical and biologic systems

+ pH and solubility

* Influence of buffering on the solubility of base
- Atalow pH: base is in the ionic form & usually very soluble in
- As the pH is raised : more undissociated base is formed when the

Base soln. should be buffered at a sufficiently low pH for st

>

27. Buffer in
pharmaceutical and biologic systems

(Example)

GOAL: Compute the mole percent of free base presg

28. Buffer in
pharmaceutical and biologic systems
+ Example C11H16N202+ H,O
= CuHi6N202H° + OH

(Pilocarpine base) (Pilocarpine ion)

At pH 7.4 > At pH 4.0
7.4= 14-7.15 + log 4.0 = 14 — 7.15 + log

29. Buffered isotonic solution

Red blood cell

NaCl solution

30. Types of Tonicity

NaCl 0.2% NaCl 0.9% NaCl 2%

solute » solute solute —solute solute < solute
Inside outside Inside outside Inside outside

swelling equilibrium shrinkage

Isotonic Hypotonic

NA y
000. . =
a DB a

Hypertonic medium

Effect of different solutions on blood cells

31. Buffered isotonic solution

e The term Isotonic should be restricted to
solutions having

e Isotonicity value...the concentration of an aqua

32. Measurement of tonicity

e Hemolytic method

... apply red blood cells
...based on the fact that a hypotonic soln. liberates oxyhemoglobin in di

e determine colligative properties (chapter 5)

... modifications of the Hill-Blades Technique
...based on a measurement of the slight temp. differences arising from q

Tr = 0.52 °C (Freezing point lowering of human blood

33. Calculating Tonicity Using Liso values

34. Calculating Tonicity Using Liso values

e The Van't Hoff expression (Chapter 6)

an Ti | Ic

S = “7

Conc. that is isotonic

35. Method of adjusting tonicity and pH

Class | ...add Sod. Chloride to lower the
freezing point of soln. to -0.52°
(D Cryoscopic method
@) Sodium chloride equivalent method

Class ll ...add Water to form an isotonic soln.

(D White-Vincent method
@) Sprowls method

36. Class | methods

e Cryoscopic method (U 37324)
(Example)
How much NaCl is required to render 100mL of a 1% soln. of apo

=> A Tr of NaCl soln : 0.52°(Isotonic with blood)
0.9%

A Tr of apomorphine HCI soln : 0.08° (from table)

o 1%

to reduce the freezing point by an additional 0.44°(0.52-0.08)
E) A Tr of NaCl soln : 0.58°

1%

1(%)/X = 0.58/0.44 ; X = 0.76 (%)

Dissolve 1 g apomorphine HCI + 0.769 NaCl/make 100mL so

36

37. 2-NaCl equivalent method

+ NaCl equivalent “E”
Amount of NaCl that is equivalent to(i.e., has the
same osmotic effect (same f.p.d) as ) 1 gm of drug
- 1% calculate E a
» „nd add NaCl to reach 0.9%

38. How to calculate Ey.cı ?

ATf = Le

wt.
ATE, = + 5 ATf, acl = Ly ”
drug Lo M.wt xv NaCl (NaQ)

Wy,
x NaCl
Mwt ja XV war

drug drug

Wearug = Wa ci

x = L y X
so(drug so(Na CI)
M.wt drug X V dus M.wt naci XV

L,

NaCl
Wl drug = lgm Wena = Ea M-wt yaoi 58.45

Loa) = 3-4

‘NaCl —

1 TL (drug)
M.wt

drug

39. Class | methods

e Sodium chloride equivalent(E) method
(3 Et) by Mellen & Seltzer

1g drug tonicity = Eg NaCl tonicity

E : weight of NaCl with the same freezing point depression as 1g of th

¢ AT: = Liso .C 61 8/ molcla was
19/MW

ATi = Liso é
3.4 58.45

E = 17. Liso/ MW

40. Class || methods
e White-Vincent method

(Example)

GOAL: make 30mL of a 1% soln. of procaine HCl isoton

41. Class || methods

e Steps for White-Vincent method
@ Weight in grams of drug(0.3 g) + Sod. Chloride equiva

0.9 g/100mL = 0.063 g/ V

V = 0.063 +» 100/0.9

V=7.0 mL

Add isotonic-buffered diluting soln. to complete

V=weEe 111.1

42. Class || methods
eWhite vincent method

ater

0.9%NaCl add 0.9%NaCl

isotonic
0.3g drug
(E=0.21)
Isotonic buffered sol.

43. Class || methods
e Sprowls method

bp solution)