The document classifies pharmaceutical products into solids, semi-solids, liquids, and gases and describes common examples of each type such as tablets, creams, syrups, and inhalers. It then discusses the manufacturing process for solid oral dosage forms like tablets and capsules which involves steps like blending, granulation, compression, and coating. Key equipment used includes drying equipment, tablet presses, coating machines, and quality control instruments.

1. Classification of Pharmaceutical
products and processing
 classification of pharmaceuticaldosage forms
 solids
 semi solids
 liquid forms
 gas forms

2.  solids maybe tablets and capsules.
 semi solids are in cream,gel or in pate form.
 liquid are in syrup or in solution form.
 gas maybe inhalers or in aerosol form.
SOLID FORM
oral solid dosage forms are some of the most popular and convenient methods of drug delivery.
They can be produced in a non-sterile environment with the high volume of products produced in these dosage forms.

3. TYPES OF SOLID DOSAGE FORMS
 TABLETS
 CAPSULES
 POWDER
 LOZENGES

4. TABLETS
 They are unit solid dosage forms consisting of the active ingredient and suitable
pharmaceutical expients.
They may vary in size, shape, weight, hardness, thickness, disintegration and characteristics
and in other aspects.
CAPSULES:
They are unit solid dosage forms of consisting of gelatin shell that breaks open after the
capsule has been swallowed and releasing the drug.

5. CAPSULES
 TYPES
 Hard-shell gelatin capsule
 Soft-shell gelatin capsule
 1. SOFT GELATIN;
 Manufactured in one piece with drug usually in liquid form
inside the shell e.g;fat soluble vitamins and E etc.

6. 2. HARD SHELL
 Manufactured in two pieces that fit together and hold the drug, either in powdered or
granular form.
 LOZENGES
 Tablets formed from hardened base or sugar and water containing drug and other flavors.
 they are designed to dissolve slowly in the mouth and release the drug topically to the
tissues of mouth and throat they are not to be swallowed.

7. POWDER
 They are bulk solid dosage forms consisting of two or more medicament meant for internal use.
 The size of the powder determines the effective physiological properties.
SEMI-SOLID FORMS
They contain both liquid and solid dosage forms that are too soft in structure to quality for solids but too thick to
be considered liquid. They are meant for typical application.

8. PHARMACEUTICAL PROCESS
It is the formation of drugs which involves the unit operations.
Types of unit operation
i. Size reduction
ii. Blending
iii. Drying
iv. Tablet compression
v. Coating
vi. Dry granulation

9. Equipment’ s Used
i. Drying equipment
ii. Tablet machine
iii. quality control machine
iv. Coating machine
v. Granulator
vi. Weighting machine
vii. Mixing equipment’ s
viii. Size reduction equipment

10. Steps involved in tablet formation
 Active pharmaceutical ingredients are bulk drugs that are
pharmaceutically active and generate a desired pharmacological
effects.
Excipients:
 They are pharmaceutically inactive and they act as a carrier .

11. POWDER BLENDING
 Powder are mixed using a blender to obtain to obtain a uniform and
homogenous powder.
 A wide range of excipients may be blended to create the final blend
used to manufacture the solid dosage form in pharmaceutical industry.

12. GRANULATION PROCESS
 Granulation process transfers fine powder into the free flowing ,dust free
granules that are easy to compress.
 There are three methods of Granulations
 Wet Granulation
 Dry Granulations
 Direct Granulations

13. WET Granulations
 It is a widely used methods for the production of compressed.
 It is essentially a process of size enlargement
 Greater probability of meeting the physical requirements for tablet
formation

14. DRY GRANULATION
 The formation of granules by compacting powder mixtures into large
pieces or compacts which is subsequently broken down or sized into
granules is a possible granulation methods.
 It is not widely used methods.
 It is generally achieved by roller compaction.

15. DIRECT GRANULATION
 Direct Compression involves the direct compression of powdered
materials into tablets without modifying the physical nature of the
materials itself.
 It has great importance because it is cheapest ones.
 It also avoids many problems.

16. DRYING AND DRY SCREENING
 .Screened wet granules need to be dried for a particular time period in a
fluid bed dryer at controlled temperature not exceeding 55C.
 TABLET COMPRESSION :
 This step involves in the compression of granules into a flat or convex
,round or unique shaped tablets.

17. COATING
 Tablets are coated if there is need to mask the unpleasant taste or odour
of some drud substances.

18. Defects in compression tablets
i. Poor mixing
ii. Low hardness
iii. Weight variation

19. Synthesis Of
Paracetamol

21. Paracetamol also known
as acetaminophen or APAP, is a medicine used
to treat pain and fever. It is typically used for
mild to moderate pain relief. Evidence for its
use to relieve fever in children is mixed .It is often
sold in combination with other medications,
such as in many cold medications. In
combination with opioid pain medication,
paracetamol is also used for severe pain such
as cancer pain and pain after surgery .It is
typically used either by mouth or rectally, but is
also available intravenously .Effects last
between 2 and 4 hours.

22. Chemical properties
 Paracetamol molecule polar surface area
 Paracetamol electrostatic potential map
 Paracetamol consists of a benzene ring core, substituted by
one hydroxyl group and the nitrogen atom of an amide group in
the para (1,4) pattern.[The amide group is acetamide (Ethan amide). It is
an extensively conjugated system, as the lone pair on the hydroxyl
oxygen, the benzene pi cloud, the nitrogen lone pair, the p orbital on
the carbonyl carbon, and the lone pair on the carbonyl oxygen are all
conjugated. The presence of two activating groups also make the
benzene ring highly reactive toward electrophilic aromatic substitution. As
the substituents are ortho, para-directing and para with respect to each
other, all positions on the ring are more or less equally activated. The
conjugation also greatly reduces the basicity of the oxygen's and the
nitrogen, while making the hydroxyl acidic through delocalization of
charge developed on the phenoxide anion.

23. Synthesis of Paracetamol
In the laboratory, paracetamol is easily prepared by nitrating phenol
with sodium nitrate, separating the desired p-nitro phenol from
the ortho- byproduct, and reducing the nitro group with sodium boro
hydride. The resultant p-aminophenol is then acetylated with acetic
anhydride. In this reaction, phenol is strongly activating, thus the
reaction requires only mild conditions nitration The industrial process is
analogous, but hydrogenation is used instead of the sodium boro
hydride reduction

24. Procedure
1. Add 2.1 grams of 4-aminophenol into the round-
bottomed flask.
2. Using your 25 mL measuring cylinder, measure 18 mL of
water and add this to the flask.
Add a magnetic follower to the round-bottomed flask.
3. Carefully clamp the flask at the neck and position it in
the metal Dry Syn block which should be placed on the
stirrer hotplate. Stir the reaction mixture using a magnetic
follower. Do not apply heat at this stage
. 4-. Assemble the apparatus for reflux as shown in the
diagram below. Tip: Do not clamp the condenser

25. 5. Using a Pasteur pipette, measure 3 mL of
ethanoic
anhydride (also known as acetic anhydride)
into a
10 mL measuring cylinder. Add this to your
mixture
by lifting the condenser and adding directly to
the
round-bottomed flask.
6. Replace the condenser and switch on the
heat to
your hotplate (set the dial to about 120°C).
Make sure there is water going through your
condenser.
7. The reaction is heated at reflux for 15 minutes,
stirring continuously. The reaction mixture should
become colorless.
8. After refluxing for 15 minutes, switch off the
heat

26. 11. filter the precipitate (using a Buchner funnel),
washing with small amounts of cold, distilled water.
12. After drying, the crude product should be
placed in a clean 100cm3 conical flask and
recrystallized by heating until it just dissolves in
approximately 20ml of water.
Cool the flask in ice until crystals of the purified
paracetamol appear.
Filter the crystals under vacuum, dry in a warm oven
and then record the melting point and compare with
standard paracetamol tablets (~170oC). Repeat
recrystalisation process to achieve a more purer
product

27. Synthesis of Aspirin

28.  Aspirin act as an analgesic, antipyretic (Something that reduces fever or
quells it), Anti-inflammatory also inhibit platelet aggregation & prolongs
bleeding time, because of its effect on G.I.T(gastrointestinal tract) it is
contraindicated ( Anything (including a symptom or medical condition) that is a
reason for a person to not receive a particular treatment or procedure because it
may be harmful) in peptic ulcer, in this case we use paracetamol .
 Aspirin is not given to children because is may cause raye’s syndrome.

29. Introduction :
 Aspirin (acetyl salicylic acid) is a widely used drug in modern
society.
 Salicylic acid which is a constituent of certain plant is itself an
analgesic & was originally administered as sodium salicylate,
since salicylic acid has an irritating effect on the stomach,
chemists thought of a modification which would retain its
properties while decreasing the adverse side effects.
 Conversion to the ester satisfied this requirement& aspirin
proved to be as effective as sodium salicylate without the
irritation of phenolic compound.
 Aspirin however hydrolyzed to salicylic acid in the alkaline
media of the intestine by esterase enzyme.

30. substitution)

31. Esterification
 Aspirin is prepared in our lab by acetylating of salicylic acid
with acetic anhydride in the presence of H2SO4 as catalyst.

32. Procedure:
1-Place 3 gm of salicylic acid in 100 ml E.f. and add with constant stirring 6 ml
of acetic anhydride followed by 1 ml of conc. H2SO
2- Stir the mixture gently observing the rise in temp. to 70-80 oC.
While the salicylic acid dissolves, after 15 minutes the solution cools by itself
and a solid mass of aspirin forms
3-Pour 35 ml of ice-cold water over the contents of the flask to hydrolyze
excess acetic anhydride and to complete the ppt of aspirin
4- Collect the crude aspirin using a Buchner funnel and wash with ice-cold
water, air-dry the product and calculate the yield
5- Perform FeCl3 test on produced aspirin

33. Identification test of
Aspirin:
 Ferric chloride test;
 The presence of phenolic group in a compound is indicated by
the formation of violet iron complex when treated with ferric
chloride solution
 Aspirin ------------► give –ve result with FeCl3 due to absence of
phenolic group
 Salicylic acid--------► + ve result

34.  What is le chatelier’s principle?
 "If an equilibrium is subjected to a change of concentration, pressure or
temperature, the equilibrium shifts in the direction that trends to undo the
effect of the change”
 Why cold water is used in Aspirin washing?
 Aspirin, like many other substances, is more soluble in hot water than in cold water.
Therefore, to maximize the amount of crystals, it is best to cool the mixture as
much as possible.
 What are the methods which are used to assess
aspirin purity?
 Spectrophotometers are a reliable and economical way to keep the purity of Aspirin
consistent throughout the manufacturing process. The purity and amount of
acetylsalicylic acid in aspirin can be measured using a Visual Spectrophotometer.

35. Erythromycin

47. Streptomycin
(PRODUCTION & USE)

48. Introduction
Streptomycin:
Streptomycin is broad spectrum anti
-biotic (antimayobacterial) belonging to
oligosaccharides antibiotic or aminoglycoside
family.
It is active against gram negitive bacteria.

49. Uses
A number of bacterial infections can be treated by streptomycin. Such as:
 Tuberculosis
 Mayobacteriumavium complex
 Endocarditis
 Brucellosis
 Burkholderia infection
 Plague
 Tularemia
 Rat bite

50.  Streptomycin is active against Gram negitive bacteria. It is used to
treat Tuberculosis caused by Mycobacterium tuberculi.
 It is also used therapeutically in thr treatment of infectious diseases
caused by Gram negitive bacteria, specially organisms which are
resistant to penicillin.
 Prolonged treatment by Streptomycin at high dose can produce
neurotoxic reactions such as hearing impairment, los of balance
maintenance in man.

51. Origin of
streptomycin
Streptomyces griseus-
belongs to genus Streptomyces
commonly found in soil.
It is gram positive bacteria.
It is well known producer of antibiotic
and secondary metabolites.
Streptomyces griseus under
microscope

52.  They produce grey spore masses and grey-yellow reverse pigments when
they grow as colonies.
 The specification of this organism is that it grows in wide range pH ( from 5
to 11).

53. History
 Streptomycin was first isolated on October 19,1943 by Albert Schartz, a
PHD student on laboratory of Selman Abraham Waksman at Rutgers
University.
 Waksman and his laboratory staff discovered several antibiotics including
actinomycin , clavacin,streptothricin,neomycin etc.
 Streptomycin was first antibiotic cure for Tuberculosis.

54. Mechanism of action
Streptomycin is protein synthesis inhibitor.
It binds the 16S rRNA of 30S subunit of bacterial ribosome,interfering with binding of
formyl-methionyl tRNA to 30S subunit.
This leads the complete or partial inhibition of protein synthesis and eventually
death of microbial cells.
Human have ribosomes which are structurally different from that of bacteria,so
drugs does not have any effect on human cells.

55. Biosynthesis of Streptomycin
 In biosynthesis of streptomycin more tha 30 enzymatic steps are identified.
 Glucose 6-phosphate takes 3 independent routes to produce streptidine 6-
phosphate,L-dehydrostreptose and N-methyl glucosamine.
 The former two compounds condense to give an intermediate which combines
with methyl glucosamine to produce dihydro-streptomycin-6-phosphate.

56. Streptomycin is directly derived from glucose.
Though the enzymes involved in the synthesis of
N-methyl glucosamine are not yet known, it is
expected that about 30 enzymes take part in
the conversion of glucose into streptomycin

57.  Woodruff and Mc Daniel (1954) suggested medium consisting of soyabean meal
(1%), glucose 1% and sodium chloride (0.5%), Hocken hull (1963) recommended
the medium consisting of glucose (2.5%), soyabean meal (4.0%), distillers dry
soluble (0.5%) and sodium chloride (0.25%) and pH 7.3-7.5 for production of
streptomycin by S. griseus.

58. This process involves following 3 steps:
 Innoculum production
 Preparation of media
 Fermentation
 Harvest and recovery
 Byproduct

59. 1-Innoculum production
 Spores of S. griseus maintained as soil stocks or lyophilized in a carrier such
as sterile skimmed milk, is employed as stock culture. The spores from
these stock cultures are then transferred to a sporulation medium to
provide enough sporulated growth to initiate liquid culture build-up of
mycelial inoculum in flasks or inoculum tanks. After sufficient mycelial
growth, it is fed to production fermenter.

60. 2-Preparation of media
 A production medium contains carbon source and nitrogen source. Glucose is one of
the best carbon sources which helps in the greater yield of streptomycin, because it
provides basic carbon skeleton for the streptomycin production. Apart from glucose,
fructose, maltose, lactose, galactose, mannitol, xylose and starch can also be used as
carbon source. Polysaccharides and oligosaccharides generally give low yields.
 Peptones, soya extracts, meat extract, the residue from alcohol distillation, ammonium
salts, nitrates and glycine may be used as nitrogen source. Magnesium, calcium,
potassium, boron and molybdenum may be used as mineral source along with
sulphates, phosphates and chloride

61.  Phenylacetic acid, L-naphthalene acetic acid may be added as growth
stimulating compounds. It is better to add proline into the medium which helps in
high streptomycin production. Fats, oils and fatty acids may also be used along
with glucose. If necessary antioxidants such as sodium sulphate or starch or agar
may also be added into the medium. There is no need of precursor in the
production of streptomycin.

62. 3-Fermentation
 Sterilized liquid medium with all the above substances is fed to the production fermenter.
Appropriate volume of inoculum (4-5%) is introduced into it. The optimum fermentation
temperature is in the range of 25 to 30°C and the optimum pH range is between 7.0 and 8.0.
High rate of streptomycin production, however, occurs in the pH range of 7.6 to 8.0.
 The process of fermentation is highly aerobic and lasts approximately for 5 to 7 days and
passes through 3 phases:

63. It takes about 24 hours to 48 hours. Rapid
growth and formation of abundant
mycelium occurs during this phase. The pH
rises to 8.0 due to release of ammonia into
medium, due to proteolytic activity of S.
griseus. Glucose is utilized slowly and little
production of streptomycin is witnessed.
(a) The First Phase

64. (b) The Second Phase:
It lasts for 2 days. Streptomycin
production takes place at a rapid rate
without increase in the mycelial growth.
The ammonia released in the first phase
is utilized, which results in the decrease
of pH to 7.6-8.0. Glucose and oxygen
are required in large quantity during this
phase.

65. (c) Third Phase:
Cells undergo lysis, releasing ammonia
and increase in the pH, which falls
again after a period of continuous
streptomycin production. Requirement
of oxygen decreases and the contents
of the medium including sugar get
exhausted. Finally streptomycin
production ceases. A yield of 1200
micrograms per milliliter of
streptomycin is obtained.

66. (iv) Harvest and Recovery:
After completion of fermentation the
mycelium is separated from the broth
by filtration. Streptomycin is recovered
by several methods.
But the one which is generally
employed is described below:

67. The fermentation broth is acidified, filtered and
neutralized. It is then passed through a column
containing a cation exchange resin to adsorb
the streptomycin from the broth. The column is
then washed with water and the antibiotic is
eluted with hydrochloric acid or cyclohexanol
or phosphoric acid. It is then concentrated at
about 60°C under vacuum.

68. The streptomycin is then dissolved in methanol and
filtered and acetone is added to the filtrate to
precipitate the antibiotic. The precipitate is again
washed with acetone and vacuum dried. It is
purified further by dissolving in methanol. The
streptomycin in pure form is extracted as calcium
chloride complex.
(v) Byproduct Vitamin B12:
Vitamin B12 is produced as a byproduct which
will not affect adversely the yield of
streptomycin.

69. 69

70. 70

71. 71

72. 72

73. 73

74. 74

75. 75

76. 76

77. 77

78. 78

79. 79

80. 80

81. 81

82. 82

83. 83

84. 84

85. 85

86. 86

87. 87

88. 88

89. 89

90. 90

91. 91

92. 92

93. 93