Medication-related

problems.
 A medication-related problem
is an event or circumstance
involving medication therapy
that actually or
potentially interferes with an
optimum outcome for a specific
patient.
Dispensing Errors
 error of interpretation of doctor’s
prescription and inaccurate
calculation of doses
 refers to medication errors linked
to the pharmacy and includes error
of commission ( dispensing the
wrong drug and dose ) and those of
omission ( failure to counsel on safe
of drugs )
Causes of errors in the Pharmacy setting:
1. Too many telephone calls
2. Overload/ usually busy day
3. Too many customers
4. Lack of concentration
5. No one available to double check the purchase
medicines
6. Staff shortage
7. Similar drug names
8. No time to counsel
9. Illegible prescription
10. Misinterpreted Prescription
Medication errors failure to follow
label Instruction
1. Failure to shake well
2. Crushing medications ( eg. “do not crush”
Extended release tablets, and coated tablets
3. Medication taken with food or antacids ( eg
NSAID + Food , Ciprofloxacin + Food )
4. Sublingual tablets which should not be swallow
5. Use of inappropriate solvents ( eg. anti cancer
drugs, oxiplatin must reconstitute with 5%
dextrose only, Suspensions like antibiotics must
followed specific amount of solvents
Following categories of
medication-related problems:
1.Untreated indications.
The patient has a medical problem that
requires medication therapy (an indication for
medication use) but is not receiving a
medication for that indication.
2. Improper drug selection.
The patient has a medication indication but is
taking the wrong medication.
3. Subtherapeutic dosage.
The patient has a medical problem that is
being treated with too little of the correct
medication.
4. Failure to receive
medication.
The patient has a medical problem that is
the result of not receiving a medication
(e.g., for pharmaceutical, psychological,
sociological, or economic reasons).

5. Overdosage.
The patient has a medical problem that is
being treated with too much of the correct
medication (toxicity).
6. Adverse drug reactions.
The patient has a medical problem that is the
result of an adverse drug reaction or adverse
effect.

7. Drug interactions.
The patient has a medical problem that is the
result of a drug–drug, drug–food, or drug–
laboratory test interaction.

8. Medication use without

indication.
The patient is taking a medication for no
medically valid indication.
Classifications of Medication Related Problems

1.Adverse reaction(s)
Patient suffers from an adverse drug event
2. Drug Choice Problem
Patient gets or is going to get a wrong (or no drug) drug for
his/her disease and/or condition
3. Dosing problem
Patient gets more or less than the amount of drug he/she
requires
4. Drug Use Problem
 Wrong or no drug taken/administered
5. Interactions
There is a manifest or potential drug-drug or drug-food
interaction
Domain Causes:
Drug/Dose Selection
The cause of the DRP can be related to the selection of the drug and/or dosage
schedule
Drug Use Process
The cause of the DRP can be related to the way the patient uses the drug, in spite
of proper dosage instructions (on the label)
Information
The cause of the DRP can be related to a lack or misinterpretation of information
Patient/Psychological
The cause of the DRP can be related to the personality or behaviour of the patient.
(Pharmacy) Logistics
The cause of the DRP can be related to the logistics of the prescribing or
dispensing mechanism
1. Drug/Dose selection
Causes:
 Inappropriate drug selection
 Inappropriate dosage selection
 More cost-effective drug available
 Pharmacokinetic problems, including ageing/deterioration
in organ function and interactions
 Synergistic/preventive drug required and not given
 Deterioration/improvement of disease state
 New symptom or indication revealed/presented 1
 Manifest side effect, no other cause
2. Drug use process
Inappropriate timing of administration and/or
dosing intervals Drug underused/ under-
administered
Drug overused/ over-administered
Therapeutic drug level not monitored
Drug abused (unregulated overuse)
Patient unable to use drug/form as directed
3. Information
 Instructions for use/taking not known
 Patient unaware of reason for drug treatment
 Patient has difficulties reading/understanding
Patient Information Form/Leaflet
 Patient unable to understand local language
 Lack of communication between healthcare
professionals
4. Patient/Psychological
 Patient forgets to use/take drug
 Patient has concerns with drugs
 Patent suspects side-effects
 Patient unwilling to carry financial costs
 Patient unwilling to bother physician
 Patient unwilling to change drugs
 Patient unwilling to adapt life-style
 Burden of therapy
 Treatment not in line with health beliefs
 Patient takes food that interacts with drugs
5. Logistics
Prescribed drug not available
Prescribing error
Dispensing error (wrong drug or
dose dispensed)
Interventions:
1.Prescriber :
Prescriber informed only
Prescriber asked for information
Intervention proposed not approved by
Prescriber
Intervention proposed outcome unknown
2. Pharmacist ( Drug Level )
Drug changed to …
 Dosage changed to ….
 Formulation changed to …..
Instructions for use changed to …..
Drug stopped
 New drug started
Recommendations
Outcomes.
It is the goal of pharmaceutical care to improve an individual
patient’s quality of life through achievement of definite
(predefined), medication-related therapeutic outcomes. The
outcomes sought are
1. Cure of a patient’s disease.
2. Elimination or reduction of a patient’s symptomatology.
3. Arresting or slowing of a disease process.
4. Prevention of a disease or symptomatology.
IMMISCIBILITY
 When two such ingredients are combined resulting in a non-
homogenous product, such ingredients are called
immiscible to each other and the phenomenon is called
immiscibility.

 This manifestation appears clearly in emulsions, creams,

lotions, some types of ointments. Separation in two phases
is noticed in this pharmaceutical dosage form.

 Storage must be in room temperature to prevent

separation.
The following factors lead to immiscibility
1. Incomplete mixing
2. Addition of surfactant with
3. Unsuitable concentration
4. False time of addition
5. Unsuitable for the type of emulsion
6. Presence of micro – organisms
Some bacteria grow on constituents of mixture
eg. Gelatin Gum Arabic
7. Others produce enzymes which oxidize the surfactant.
8. Temperature
9. Oils and water are immiscible with each other which shows physical incompatibility
Example - Castor oil emulsion
Rx
Castor oil – 15ml
Water – 60ml
Causes: -In this prescription castor oil is immiscible with water due to high
interfacial tensions, which is a sign of incompatibility.

Remedy: -To overcome this type of incompatibility emulsification is necessary

with the help of an emulsifying agent. The corrected prescription is Castor oil
emulsion

Rx
Castor oil – 15ml
Acacia – 2% W/V
Water– up to 60ml
Factors affecting Solubility:
1. Dehydration or Salting out
2. Change solvent System
3. Temperature Change
4. Physical Complexation
1. Dehydration or Salting out
 Happens when adding an electrolyte to an aqueous solution with slightly
soluble electrolytes. Since electrolytes has more affinity to water molecules:
Examples:
 Separation of alcohol from hydro alcoholic vehicle on addition of
electrolytes
 salting out of electrolytes from an aqueous solution by addition alcohol
2. Change Solvent System
 Usually happens when mixing organic solvents ( liquid
petrolatum ) with aqueous medium results in
precipitation. Knowledge and understanding of
solubility principles can predict solubility of materials
Example - Lotion of compound tincture of benzoin
Rx
Tincture benzoin compound – 5g
Glycerin – 10ml
Rose water up to 100ml

Causes: - Tincture benzoin compound contain resins.

This change in solvent system results in an
unavoidable precipitate.

Remedy: - Addition of tincture with rapid stirring yields

a fine colloidal dispersion. So there is no need of any
suspending agents.
3. Temperature Change
 Endothermic Substances
Their solubility decreases as temperature decreases ( below room
temperature )
example : KI, Boric Acid

 Exothermic
Their solubility decreases as the temperature increases ( above room
temperature )
Example: Calcium hydroxide
4. Physical Complexation
 Present in organic compounds due to formation of
coordinate compounds or molecular complex that
could decrease solubility
 Bonded together by coordinate bond , not ionic or
covalent
Other factors affecting prescribed agent in
vehicle and may render it less soluble:
1. Change in pH
2. Milling
3. Surfactants
4. Chemical reactions
5. Complex formation
6. Co – solvent
Solubility Guide
Inorganic Compounds:
Most of their binding are ionic or covalent in nature which
makes them soluble in water and semi polar solvents such as
alcohol and acetone.
Parameters affecting solubility ( hydration of energy factors )
1. Lyotropic Number
2. Ratio of change of ionic radius
3. Heats of hydration
A. ALKALI METALS CATIONS
 NH4 , Li , Na, and K
 Solubility of salts is of decreasing order ( Increase MW , decrease
solubility ) Example: LiCl is much more than KCl. If combined with
Multivalent anions its solubility will ( KCl + K3PO4 is trivalent )

B. ALKALINE EARTH METALS

 Ba, Sr, Ca, Mg+2
 this group can still follow the order for ( Alkali Metals ) univalent cations
but not as well. They form water soluble salts with univalent anions for
OH and HCO3 ions. If combined with Multivalent anions its solubility
will also decrease
C. Heavy Metals
 Zn and Hg
 Zinc forms insoluble OH with water that are soluble with excess base OH or H
by formation of soluble anions or cations. It forms soluble salts with univalent
and divalent anions but hydrolyzes in aqueous solutions forming oxy salts
which are insoluble in water.

D. Boron and Al.

 Most Borates are water soluble however in alkaline medium if forms insoluble
borates.
Al common salts Cl, SO4, PO4 and OH and double sulfate with K or NH4
( alums ) ex. AlKSO4
 Univalent or Divalent anions forms soluble salts but forms insoluble salts with
trivalent anions.
E. Sn and Pb
 Sn exist in + 2 , + 4 with +4 more stable. Only salts with use in pharmacy
is Stannous fluoride ( dental caries ). It is freely soluble in water but
hydrolyzes to insoluble basic slats or OH.
 Pb exist in + 2 , + 4 with + 2 being more stable. Lead salts of acetate and
subacetate are rarely used. They are water soluble but tend to to hydrolyze
rapidly to form insoluble salts.

F. As and Bi
 Bi salts their insoluble oxy salts are used in pharmacy. These salts tens to
hydrolyze in aqueous system.
G. Fe
 exist in +2 and +3 being stable. Fe tends to form soluble salts which readily
hydrolyze to insoluble OH. PO4 and CO3 salts are insoluble
 complex Fe salts used to avoid hydrolysis and precipitation

H. Non – metals S and I

 Sulfur available forms precipitated or sublimed. Insoluble in water in water
or most solvents.
 Iodine is insoluble in water. Iodides ( KI) are used to make it more soluble or
to dissolve large amounts of iodine
ORGANIC COMPOUNDS
Organic Compounds are soluble in water provided they contain
groups which are capable of :
Hydrogen Bonding
Being Polarized
Ionized

Extent of their solubility is based on:

Type of water – organic molecule bonding ( forces )
Ratio of polar to non – polar portions od the molecule
A. Hydrocarbons
 liquid petrolatum
 Because most these are no – polar , they are only in non – polar solvents
and are not capable of associating with water.

B. Compound solubilized through hydrogen bonding and

polarization
 ROH, C6H5OH, R –COOH , R-HN2, R – CHO, RC=O and R – COO are
water soluble as a result of their ability to form hydrogen bond
 Remember : Ratio of polar group to non – polar group. 1 -3 soluble, 1:5
slightly, 1:5 slightly soluble and 1.6 < insoluble.
C. Monofunctional Alcohols.
CH3CH2OH and Isopropyl alcohols possess complete miscibility with
water. Most of these alcohols acts as co – solvents with water.

D. Polyfunctional ROH
 Additional OH groups serve to increase water solubility as long as the
ratio of P – NP groups is 1: 3 : 4

E. Glycols and carbohydrates

 They exhibit water solubility of the ratio of P-NP groups. ( Glycerin,
ethylene glycol, polyethylene glycols., gums, as acacia, agar , and
tragacanth , CH3 and CMC.
F. C6H5OHs
 Benzene ring and 1 – OH group – slightly water soluble. Increase in OH
group without increase in C atoms increases solubility. Resorcinol ( Phenol +
1 OH group more soluble.

G. R-COOH
 These compounds depend on H bonding for their water solubility rather
than on their limited ionization. Monofunctional acids with ratio of polar
group to non – polar group 1:3 , 1.5 slightly and if 1.6 or greater is insoluble.

 Aromatic acids like benzoic acids with 5 carbon group is slightly soluble.
The rule stated above is applicable but by 0.4% less then might be predicted
from the general rule.
H. R – NH2
 these also depend on their ability to H bond for their water
solubility and as the ratio C atoms to amine groups increases, water
solubility drops off sharply.

I. RCHO
 most pharmaceutically available RCHOs like formaldehyde and
C 2H 3Cl 3O 2 possess considerable water solubility via hydrate
formation. Paraldehyde , although it is an acetal, can regenerate
acetaldehyde under certain conditions and thus exhibits
characteristics of this compound.
J. RC=O
 acetone and camphor are examples of pharmaceutical
ketones. Acetone is completely miscible with water while
camphor is insoluble with water but soluble in ethanol

K. Esters
 the lowest of polyfunctional esters are very soluble in
water ( methyl acetate, resorcinol monoacetate ) Higher
esters on the other hand are water – insoluble ( Phenyl
Salicylate )
Note: Solubilized substances may precipitate from it solution if a non-solvent for the
substances is added to the solution.

Alcoholic solution of resins + water =precipitated resins.

Aqueous dispersions of hydrophilic colloids
(polysaccharide mucilage + high concentration of alcohol
or salts) =precipitated colloids.
 High concentration of electrolytes causes cracking of soap emulsion by salting
out the emulsifying agents. Vehicles (one or more organic liquids) use to dissolve
medicaments of low solubility; water soluble adjuvant practically inorganic salts
may be precipitated in such vehicles.

 When tinctures containing resinous matter are added in water, resin

agglomerates forms in diffusible precipitates. This can be prevented by slowly
adding the undiluted tincture with vigorous shake. Suspension or by adding
some suitable thickening agent.
Example - Lotion of compound tincture of benzoin
Rx
Tincture benzoin compound – 5g
Glycerin – 10ml
Rose water up to 100ml

Causes: - Tincture benzoin compound contain resins. This change in solvent

system results in an
unavoidable precipitate.

Remedy: - Addition of tincture with rapid stirring yields a fine colloidal

dispersion. So there is no need of any
suspending agent.
Example-Insufflations
Rx
Menthol – 5g
Camphor – 5g
Water – 60ml
Causes: - This mixture is a physical incompatibility because both the ingredients in the
prescription are liquefiable of mixed together.

Remedy:-These substances can be dispensed by any one of the following method. Triturate
together to form liquid and mixed with an absorbent (light kaolin, magnesium carbonate) to
produce the following powder . The individual medicaments is powdered separately and mixed
with an adsorbent and then combined together tightly and filled in a suitable container

Hence the corrected prescription is

Rx
Menthol – 5g
Camphor – 5g
Light kaolin– 0.2
Gelling, Granulation , Cementation of
liquids
Bismuth subnitrate plus acacia as suspending agent
Alcoholic solutions and acacia

Evolution of Gases
Effervescence
Liberation of Gas Nitrous Oxide from one zinc and concentrated nitric acid

Change in color
 Antipyrine + Ethyl nitrate
Cherry syrup + Alkalies
Liberation of Iodine from Iodide in acid medium
CHEMICAL INCOMPATIBILITY

Reaction between two or more substances which lead to change in chemical properties of
pharmaceutical dosage form. As a result of this a toxic or inactive or product may be formed
Occurrence:-
Chemical incompatibilities occur, due to the chemical properties of drugs and additive like:
1. PH change
2. Oxidation-reduction reactions
3. Acid-base hydrolysis
4. Double decomposition
5. Complex formation

These reactions may be noticed by

6. Precipitation
7. Effervescence
8. Decomposition
9. Color change
10. Explosion
TYPES OF CHEMICAL INCOMPATIBILITIES
1. Based on chemical interactions
2. Based on nature of chemical reaction
3. Based on the prescriber
4. Precipitate yielding interactions
1. Based on chemical interactions
2. Based on nature of chemical reaction

Immediate incompatibilities: - If the chemical reaction takes

place, immediately after combining the prescription ingredients,
they are called immediate incompatibilities. Hence, they should
be dispensed only after correction.

Delayed incompatibility: - When the chemical reaction proceeds

at a very slow rate and no appreciable visible change occurs
which may develop on keeping the product for along time are
called delayed incompatibility.
3. Based on the prescriber
4. Precipitate yielding interactions

Method A:
This method is suitable for diffusible precipitates following steps are
carried out.

Divide the vehicle into two portions.

Dissolve the reactants in separate portions and mix the
two portions by slowly by adding one into other with constant stirring
Method B:
This method is suitable for in diffusible precipitates following steps are carried out:

 Divide the vehicle into two portions.

 Dissolve the one of the reacting substance in one portion.
 Place second portion of vehicle in mortar and incorporate suitable amount of
compound. Tragacanth powder (2g/100ml of preparation) with constant
trituration until a smooth mucilage is produced.
 Add and dissolve the other reacting substance to the mucilage.
 Add the solution of first reactant to the mucilage slowly with constant stirring.
 A secondary label ―SHAKE THE BOTTLE BEFORE USE: should be fixed
on the container whenever method A or method B is followed in dispensing the
prescription.
Example -1: strychnine hydrochloride mixture
Rx
Strychnine hydrochloride solution -6ml
Aromatic spirit of ammonia -4ml
Water up to - 120ml
Causes:
 The quantity of strychnine hydrochloride is more than its
solubility in water (1:30).
 The aromatic spirit of ammonia contains negligible amount
alcohol.

Remedy: - Strychnine hydrochloride gets precipitated yielding

diffusible precipitate, hence follow method A.
Example -2.:Quinine hydrochloride mixture
Rx
Quinine hydrochloride -0.12ml
Sodium salicylate -4g
Water -100ml
Causes: - When quinine hydrochloride combined with the
sodium salicylates it forms quinine salicylates which is
an in diffusible precipitate.

Remedy: - Hence follow method B for precipitate

interaction