Rectal & vaginal

1. Technology of
Rectal and
Vaginal Dosage
form

3. Plan
1. General consideration.
2. Rectal suppositories,
- Physiology of rectum.
- Formulation.
- Manufacturing.
3- vaginal dosage forms
- Vaginal physiology
- Types of vaginal dosage forms.

4. Rectal preparations are intended for
rectal use in order to obtain a
systemic or local effect, or they may
be intended for diagnostic
purposes. Where applicable, containers
for rectal preparations
comply with the
requirements.

5. Several categories of rectal
preparations:
 suppositories,
 rectal capsules,
 rectal solutions, emulsions and suspensions,
 powders and tablets for rectal solutions and
suspensions,
 semi-solid rectal preparations,
 rectal foams,
 rectal tampons.

6. Suppositories – dosage form which are
solid at room temperature and melting
or dissolving at body temperature are
intended for administration in the body
cavity .
Suppositories are solid, single-dose
preparations.
The shape, volume and consistency of
suppositories are suitable for rectal
administration.

7. Rectal capsules
(shell suppositories)
are solid, single-dose preparations
generally similar to soft capsules as
defined in the monograph on Capsules
except that they may have lubricating
coatings.
They are of elongated shape, are smooth
and have a uniform external appearance.

8. Rectal solutions, emulsions and suspensions
are liquid preparations intended for rectal use
in order to obtain a systemic or local effect, or
they may be intended for diagnostic purposes.
Rectal solutions, emulsions and suspensions are supplied
in single-dose containers and they contain one or more
active substances dissolved or dispersed in water,
glycerol or macrogols or other suitable solvents.
Emulsions may show evidence of phase separation but are
readily redispersed on shaking.
Suspensions may show a sediment which is readily
dispersible on shaking to give a suspension which
remains sufficiently stable to enable the correct dose to
be delivered.

9. Rectal tampons
are solid, single-dose preparations intended
to be inserted into the lower part of the
rectum for a limited time.

10. Suppositories contain one or more active
substances dispersed or dissolved in a suitable
basis which may be soluble or dispersible in
water or may melt at body temperature.
Excipients such as
 diluents,
 adsorbents,
 surface-active agents,
 lubricants,
 antimicrobial preservatives
 colouring matter
authorised by the competent
authority, may be added if
necessary.

11. Classification
a. Rectal suppositories for adults weigh 2 gm
and are torpedo shape. Children's
suppositories weigh about 1 gm.
b. Vaginal suppositories or Pessaries weigh
about 3-5gm and are moulded in globular or
oviform shape or compressed on a tablet press
into conical shapes.
c. Urethral suppositories called bogies are
pencil shape. Those intended for males weigh
4 gm each and are 100-150 mm long while
those for females are 2 gm each and 60-75
mm in length.

12. Advantages of suppositories:
1. Suppositories are precise dosage forms containing
accurate quantities of medicament(s).
2. Suppositories have been used for systemic
distribution when the oral administration was not
suitable, as in unconscious patients, postoperative
and infants. Suppositories simplify or eliminate the
problem of infant medication.
3. Suppositories allow administration of some
medicaments, which are not tolerated orally, e.g.
medicaments which are sensitive to the gastric pH
and gastric enzymes.

13. Advantages of suppositories:
4. Suppositories permit administration of
medicament that interrupt the functionality of the
gastrointestinal tract e.g. drugs irritating to the
stomach.
5. Suppositories are useful when the stomach is not
the ideal position to receive medication such as in
case of nausea and vomiting.
6. Suppositories are suitable when local effect is
wanted as in the treatment of rectal, vaginal and
urethral diseases such as haemorrhoids.
7. Used to promote evacuation or to cleanse the
bowel in constipation and preoperative.
8. Suppositories have shown faster onset of action
than found after oral administration as the drug
is directly absorbed from the mucosa into the
venous circulation.

14. Advantages of suppositories:
8.Drugs that prone to degeneration in the
stomach.
9. Drugs destroyed by portal circulation may
bypass the liver circulation, where many
drugs subject to metabolic changes (first pass
effect).
10. Administration is easily performed by the
patient.

15. Disadavantages of Suppositories:
1. The problem of patient acceptability.
2. Difficulty in advising the patient.
3. Suppositories are not suitable for patients suffering
from diarrhea.
4. In some cases the total amount of the drug must
be given will be either too irritating or in greater
amount than reasonably cannot be placed into
suppository.
5. Incomplete absorption may be obtained because
suppository usually promotes evacuation of the
bowel and presence of faeces.
6. More difficult manufacturing process.

16. Physiology of the rectum

17. Blood Flow within the Rectum
 The length of the rectum is 15 – 20 cm.
 The rectum is divided into two sections.
- The anal canal
- The ampulla ( 4 times the anal canal)
 Following absorption, the therapeutic agent enters
the haemorrhoidal veins.
- Blood from the upper haemorrhoidal vein enters
the portal vein which flows into the liver.
- Blood in the middle and lower haemorrhoidal veins
enters the general circulation ( vena cava).
 Fate of absorbed drug is dependent on the area of
the rectum from which absorption has occurred.

18. Factors affecting rectal absorption
1. Site of absorption within the rectum.
2. The partition coefficient and degree of ionization of
drug.
3. The particle size of the dispersed active agent.
4. Nature of the basis is the most influential factor on
the absorption of active ingredients from
suppositories.
5. Irritation results in defecation.
6. State of rectum.

19. Formulation of rectal dosage form
 Creams
 Ointments.
 Gels.
 Solution and suspensions.
 Suppositories.

20. Formulation of suppositories
 Weight generally 1 – 4 grams. details
 Pullet – shape. Explain.
 Inert base into which the therapeutic
ingredient is incorporated ( dissolved or
dispersed)

21. Suppository bases
 Should be solid in storage temperature
and soften and melt or dissolved in the
recta fluid and thereby releasing the drug.
 Non-irritant to the rectal mucosa.
 Base should not chemically reacts with the
therapeutic agent.
 Chemically and physically stable over the
shelf life.
 Categories of suppository bases are:
1. Fatty ( oleaginous)
2. Water-miscible , subcategory is lipophilic
+hydrophilic having characters of both types.

22. Fatty bases
 Naturally occurring.
- Cocoa butter ( theobroma oil)
mixture of fatty acid esters of glycerol, stearic,
palmitic and oleic.
 Synthetic or semisynthetic higher fatty
acids esters of glycerol.
- Witespol
- Suppocire
 Hydroxyl number
 Melting properties
 Meltingpoint
 Viscosity of the melted base

23. Water soluble and water miscible bases
 Glycerol – gelatin base. Soluble.
 Polyethylene glycols - miscible

24. Other additives
 Surface active agents.( sobitan
esters)
 Agents to reduce hygroscopicity.
Colliodal silicon dioxide.
 Agents to control the melting point
of the base

25. Agents to increase the melting
point
Agents to decrease melting point
Beeswax Glycerylmonostearate
Cetyl esters wax Myristyl alcohol
Stearic acid Polysorbate 80
Stearic alcohol Propylene glycol
Aluminum mono or distearate
Colloidal silicon dioxide
Magnesium stearate
Bentonite

26. Methods of suppositories
production in industrial
1. Fusion Moulding
2. Compression Moulding
Hands moulding
is used only in the pharmacy!

27. Manufacturing of
suppositories

28. Method Fusion Moulding
It involves first melting the suppository base, and
then dispersing or dissolving the drug in the
melted base.
The mixture is poured into a suppository mold.
When the mixture has congealed, the
suppositories are removed from the mold.
The fusion method can be used with all types of
suppositories and must be used with most of
them.

29. Technological stages of industrial production of
suppositories by fusion moulding
1) Production of bases;
2) Preparation of drugs and obtaining
concentrate;
3) Introduction drugs in the base;
4) Formation (and packing) suppositories;
5) Packing of suppositories.

30. Production of bases

31. Stage of production bases:
1. Weighing components of the base.
2. In stainless steel reactor with a steam jacket and
stirrer components of base are alloyed at 60-
70°C and stirring for 40 minutes.
3. The base is filtered through a drug-filter, using
brass mesh or belting, and analyzed by point of
the melting, solidification and times of total
deformation.
4. Then it is transferred to the hardware
department.

32. Preparation of drugs and obtaining
concentrate
1. Making of the solution or suspension of
medicines:
- Water-soluble components are dissolved in
water, heated to 45 °C,
- Fat soluble components are dissolved in part of
the molted fat base.
- Substances insoluble in water and base, are
used as suspension:
Pre-crushed medicines are mixed in a reactor
with an equal number of base (or one and
half), heated to temperature of 40-50 °C.

33. Preparation of drugs and obtaining
concentrate
2. The obtained concentrate is cooled and
grinded by colloid miller or for thermo
sensitive substances - by three rolls
ointment rubber.
Furthermore, for obtaining of high quality
suspensions rotary-pulsation
apparatus, rotary-screw pumps and
other equipment can be used.
3. These concentrates are filtered
through calico, and then mixed with the
the base.

34. Introduction medicines in the bases
Concentrate is poured by the pump (through a
hose caprone sieve) into reactor (with an
anchor stirrer or turbine) for mixing with the
base.

35. Stage of formation and packing
suppositories:
Lines such as «Sarong 200 S» with direct dosing of
formed mass in the cells are formed of
polyvinylchloride films is used for fesion suppositories
with followed styling of products in bundles.

36. Suppositories production

37. Suppositories production

38. Sarong/SAAS 6 - AP/VP
Switzerland (Hünenberg)

39. Sarong/SAAS 6 - AP/VP
Switzerland (Hünenberg)

40. Stage of formation suppositories:
1. From the two vertical set rolls aluminium foil tapes or
polyvinylchloride films are served.
2. Then both tapes are formed in bowl-like halves, which are
connected in to the complete form and heat-sealed at the
temperature.
At the top of each form hole remains open for filling by a
needle for filling, which pours on molten suppository mass.
Thus, a formed from foil packaging is simultaneously used by
fusion moulds.
3. On the next position packaging is hermetically sealed.

41. From the two
vertical set rolls
aluminium foil
tapes or
polyvinylchloride
films are served.

42. Disadvantage of the fusion
method:
1. It's possible a bundle of
suppository mass into
separate layers during the
measuring and harden
especially in cases of the
insoluble ingredients with a
large density or fluid that are
not mixed with water
present.
2. This method is not suitable
for thermo sensitive
substances.

43. To prevent bundle of suppository
mass:
1. increase the viscosity of the
base.
2. Avoid high temperature at
the fusion of the mass.
3. Carry out mixing of the mass
before fusion in the mould.

44. The method of compressing is non-
thermal method of suppositories producing
by compressing of cooled mass and
crushed the mix of the base and drugs.

45. Equipment for compressing of
suppositories

46. The advantages of compressing method:
1. Is the ability to prevent the destruction of
thermostable drugs, lack of sedimentation of the
active ingredient and avoid possible
incompatibility with the molten suppository
base. This method is applicable when using
plastic bases.
2. In production of pressed suppositories do not
need to exert considerable efforts to eject
because the fat particles act as an effective base
oils in the wall layer as a result of severe plastic
leakage.

47. The advantages of compressing
method:
Compressing method is particularly suitable in the
production of suppositories with cardiac glycosides,
some thermosensitive hormones, biogenic
stimulators, because the production process to yield
high precision dosing, thermal stability of drugs/

48. Standardization of suppositories
1. Description
2. Identification and quantitative determination of
active substances and antimicrobial preservatives
3. Average mass and uniformity of mass
4. Disintegration
5. Uniformity of content
6. Melting point or a full strain
7. Dissolution
8. Impurities
9. Microbiological purity
10. If necessary, additional control acid and peroxide
numbers
11. Particle size

49. Directions of suppositories improving :
1. Lyophilized suppositories
2. Porous suppositories
3. Multilayered suppositories
4. Suppositories with film-coated
5. Painted suppositories

50. Notes
 Cocoa butter, theobroma oil; consists of a
mixture of fatty acids esters of glycerol (
strearic, palmitic,oleic).
 Incorporation of lipophilic drugs into
cocoa butter lowers the melting point
which can be increased by adding
beeswax 4% or cetyl esters wax 20%.
 Major problem regarding the use of cocoa
butter is polymorphism due to the high
content of triglyceride.

51.  Suppositories generally manufactured
using moulding method:
 Laboratory – arachis oil may be used to
lubricate the mould when using glycerol-
gelatin base. Alcohol/surfactant mixture
for cocoa butter.
 Plastic moulds do not require lubrication.
 In industry – strip moulding method.

52. Calculation of the mass base required
 Mould volume is known.
 Incorporation of drug into the base displace
equal volume of base.
 To ensure that correct volume of base is
used, the displacement value should be
calculated.
 Displacement value is the ratio of the weight
of the drug to the weight of the base being
displaced by the drug.
 Can be expressed as the weight of the drug
required to displace unit weight of the base.

53. Prepare 9 (2 gram) suppositories containing 5%
cinchcaine displacement value 1.5, calculate the final
formulae?
Wt of drug: (5/100)*2*9=0.90 gm
Wt of base displaced by 0.9 gm:
DV=wt drug/wt base displaced=1.5=0.9/wt base
displaced.
Wt of base displaced=0.9/1.5 = 0.6 gm
Wt of base required = 18 gm – 0.6 gm = 17.4 gm
 Formulae: cichocaine 0.9 gm
 base 17.4 gm

54. Vaginal dosage forms
 Local action.
 Systemic – due to the high vascular
nature.
 This route avoids the metabolism in
the liver.
 Fluid content is low under nomal
physiological conditions.

55. Advantage
 Successful in local action in the treatment
in infection and for the treatment of
hormone deficiency of vaginal atrophy.
 Systemic in certain therapeutic agents as
steroidal hormones oestradiol acetate for
the treatment of systemic symptoms of
menopause and in the long term
contraception.
- Prostaglandins for cervical ripening.

56. Disadvantages
 For systemic is not popular.
 Special applicator required.
 Advice for the administration.
 Industrial manufacturing is difficult.

57. Vaginal physiology

58.  There are ridges ( folds) called vaginal rugae
that increase the surface area hence
absorption.
 Rugae enhance the retention of the dosage
form facilitating prolonged drug release.
 The upper part of the vagina is a mucous
membrane resulting in a limited volume of
fluid within the vagina limiting the dissolution
of lipophilic drugs.
 The vagina is highly vascular, the venous
blood supply from the vagina does not enter
the portal system.

59. Types of vaginal dosage form
 Semisolid preparations.
 Tablets and capsules.
 Pessaries ( vaginal suppositories)
 Vaginal implants.

60. Semisolid formulations
 Formulation of creams, ointments
and gels are similar to topical
preparations.
 Used with applicator.
 Contains antimicrobial materials,
hormones or contraceptives.

61. Tablets and capsules
 Disintegrant may be incorporated.
 Requires the use of applicator.
 Patient should be carefully advised
on correct administration ( usually
towards the back of the vagina.

62. Pessaries ( Vaginal Suppositories)
 Formulated using gelatin-glycerol or
PEG bases.
 pH buffered to be 4.5
 Requires an applicator.
 Careful advise in administration.

63. Vaginal implants
 Vaginal implants are solid
formulations that provide a
controlled release of therapeutic
agent into the vaginal fluids and
may be used to achieve either local
effect or systemic action.
 Example is oestradiol implant that is
located adjacent to the cervix and
provides systemic absorption of
drug.

65. Test on Rectal & Vaginal Dosage forms
1- regarding suppositories, which of the following
statements are true?
a) Employed for the treatment of local disorder as
haemorrhoids.
b) May be used to deliver drugs systemically.
c) Suppositories are sterile products.
d) Suppositories are normally formulated with inclusion
of colourant.
2- regarding pessaries, which statements are true?
a) Employed for treatment of local disorder as infection.
b) May be used to deliver drugs systemically.
c) Pessaries are sterile products.
d) Are normally formulated with inclusion of
preservatives.

66. 3. Regarding physiology of the rectum, which of the
following statements are true?
a) Rectum is joined to the bottom of the sigmoid colon.
b) The rectum is divided into two sections termed as anal
canal and ampulla – the ampulla is the smaller section
c) The rectal surface area is relatively small < 100 cm2
d) Following absorption, drugs enter the systemic
circulation via haemorrhoidal vein.
4. Factors affecting absorption from the rectum
includes:
a) The pH of the rectal fluid.
b) Presence of faecal matter.
c) Presence of esterases in the rectal fluid.
d) The location of suppository within the rectum.

67. 5- regarding the formulation of the suppositories,
which are true?
a) Suppositories should melt or dissolve within he rectum
b) Weight of suppository between 1 and 4 gram
c) Concentration of the drug typically between 0.1 – 40%
d) Suppositories using oleaginous base requires addition
of preservative.
6- concerning theobrmina oil in suppositories,
which of the following statements are true?
a) It is a natural product consisting of a mixture of fatty
acid esters of glycerol.
b) It is a pure substance.
c) It exists in different polymorphic forms depending in
the processing temperature.
d) Melting point of suppository containing theobromine
may be enhanced by beeswax.

68. 7. In the formulation of suppositories, the
following excipients may be used for the following
reasons:
a) Surfactant to facilitate manufacturing.
b) Propylene glycol to reduce the melting point of base.
c) Colloidal silicon dioxide to reduce the hygroscopicity.
d) Ethanol to enhance the solubility of the drug within
the base.
8. Concerning the vaginal physiology, which are
true:
a) Vagina is highly vascular
b) Following absorption from the vagina, the drug enters
the portal system and hence metabolism occur.
c) There is high available surface area for drug
absorption.

69. 9. Concerning the vaginal dosage form, which of the
statements are true?
a) Creams and ointments can be use for vaginal
administration.
b) Pessaries are usually formulated using oleaginous
bases.
c) Vaginal tablets are generally formulated including
disintegrants.
d) Type I gels are generally used as vaginal dosage form
10. The following agents may be as the basis of
suppository formulation.
a) Triglyceride of higher saturated fatty acids.
b) Poly(acrylic acids)
c) Polyethylene glycol
d) Glucose.

70. Finished Rectal
and
Vaginal Dosage forms