The document discusses liquid sustained release systems. It describes various approaches to developing liquid sustained release formulations including suspensions, liquid crystalline phases, drug-resin complexes, in situ gel formation, microencapsulation, and emulsions/multiple emulsions. Key advantages of liquid sustained release systems are ease of administration to pediatric and geriatric patients, dose adjustment flexibility, and potentially better bioavailability than solid dosage forms. Evaluation methods for these systems include assessing properties like viscosity, drug entrapment efficiency, drug release profiles, and sterility. Potential applications mentioned include use of these formulations to deliver hormones, drugs for eye diseases, asthma medications, and others.

1. K.SRAVAN
(256212886047)
M.PHARM
Dept.of pharmaceutics
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2. INTRODUCTION
MERITS ANDDEMERITS
APPROACHES TO LIQUID SUSTAINED
RELEASE SYSTEM
METHOD OF PREPARATION
EVALUATION
APPLICATIONS

3. 3
The term “drug delivery systems’’ refer to the
technology utilized to present the drug to the desired
body site for drug release and absorption.

4. 4
Drug Delivery
Conventional Modified
Sustained
Extended
Site-specific
Pulsatile
Enteral
Parenteral
Other

5. INTRODUCTION
In the conventional therapy aliquot quantities of drugs
are introduced into the system at specified intervals of
time with the result that there is considerable fluctuation
in drug concentration level as indicated in the figure.
HIGH
LOW
HIGH
LOW

6. What is Sustain Release Dosage Form?
 “Drug Delivery system that are designed to achieve
prolonged therapeutic effect by continuously releasing
medication over an extended period of time after
administration of single dose.”
The basic goal of therapy is to achieve steady state blood
level that is therapeutically effective and non toxic for an
extended period of time.
The design of proper dosage regimen is an important
element in accomplishing this goal.

7. The difference between controlled release and
sustained release,
Controlled release is perfectly zero order release that is
the drug release over time irrespective of concentration.
 Controlled drug delivery- which delivers the drug at a
pre determined rate for a specified period of time.

8. Sustain release dosage form- is defined as the type of
dosage form in which a portion i.e. (initial dose) of
the drug is released immediately, in order to achieve
desired therapeutic response more promptly, and the
remaining(maintanance dose) is then released slowly
there by achieving a therapeutic level which is
prolonged, but not maintained constant.
 Sustained release implies slow release of the drug
over a time period. It may or may not be controlled
release.

9. Rationality in designing S.R.Dosage form.
The basic objective in dosage form design is to optimize
the delivery of medication to achieve the control of
therapeutic effect in the face of uncertain fluctuation in
the vivo environment in which drug release take place.
 This is usually concerned with maximum drug
availability by attempting to attain a maximum rate and
extent of drug absorption however, control of drug action
through formulation also implies controlling
bioavailability to reduce drug absorption rates.

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11. HISTORY
The history of controlled release technology is divided
into three time periods
From 1950 to 1970 was the period of sustain drug
release
From 1970 to 1990 was involved in the
determination of the needs of the control drug
delivery
Post 1990 modern era of controlled release
technology

12. The main AIM of preparing sustained release
formulation’s was intended to modify and improve
the drug performance by
 Increasing the duration of drug action.
 Decreasing the frequency of dosing.
 Providing uniform drug delivery.
12

13.  SRF’s describes the slow release of a drug substance
from a dosage form to maintain therapeutic response
for extended period (8-12hrs)of time.
 Time depends on the dosage form. In oral form it is in
hours, and in parenterals it is in days and months.
 Usually SRDF’s do not follow zero order release but
they try to mimic zero order release by releasing the
drug in a slow first order fashion.
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14.  Improved patient compliance
 Decreased local and systemic side effects.
 Better drug utilization.
 Improved efficiency in treatment.
 Increased bioavailability of some drugs
 Special effects: SR Aspirin gives symptomatic relief
in Arthritis in the morning.
 Economic in preparation
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15.  Dose dumping
 Reduced potential for accurate dose adjustment:
stability problems:
 Retrieval of the drug is difficult in case of toxicity /
poisoning and hypersensitive reaction.
 Higher cost of the formulation.
 Drugs having shorter half life (less than one hour) and
drugs having longer half life (More than twelve hrs)
cannot be formulated as SRDF’s
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16.  The dosage forms which are liquid in nature and are
capable of delivering the drug in a sustained manner
are called as liquid sustain release systems.
 They generally include suspensions , emulsions, gels
etc.
16

17. Mainly used for
ease of swallowing
in paedeatric and
geriatric use
Ease of
formulation
Economic in
preparation
Flexibility in dose
adjustment
Better
bioavailability
than solid dosage
forms
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18. Suspensions
Liquid crystalline phases
Drug – resin complexes
 In situ gel formation
Microencapsulation
Mesogenic molecules
Emulsions/ multiple emulsions
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19.  A method of preparing sustained-action liquid dosage forms
for various compounds is by microencapsulating the
biologically active ingredient and subsequently suspending
the microencapsulated form in a vehicle saturated with the
biologically active ingredient.
 It is possible to formulate liquid product, having sustained
action, by suspending coated granules or particles in a
suitable liquid media which has no action on the coats of the
granules. These formulation are similar to suspensions.
19

20.  Polymers used--- carbopol 934p,
ethylcellulose(suspensions), HPMC, eudragit
RL30D
 Resins used--- AMBERLITE(drug resin
complexes), carboxylated styrene crosslinked
by di vinyl benzene
 Drugs used– theophylline, proponolol,
timolol,etc
 Other materials such as oil, peptides are also
used.
20

21.  Suspensions are biphasic dosage forms in which the
solid phase is suspended in a liquid phase.
 To produce a sustained release liquid dosage form the
drug is encapsulated with in a suitable polymer and
then it is formulated as suspension using tragacanth as
suspending agent.
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22. The techniques like spray drying includes 2 different
methods for preparation of suspensions
1st methodsolution of drug and polymer are used as
feed solution (solvent used ethanol /water 80:20,
acetone)
2nd methoddispersion of drug in polymer solution
was feed solution( solvent used methylene chloride)

23.  Among sustained-release drug delivery systems,
microcapsules have received much attention
because of uniform distribution in GI tract
which leads to uniform absorption and
decreasing risk of local effects on GI tract.
 Another advantage of microparticulate systems
is their feasibility to be Incorporated into liquid
dosage forms such as suspensions.
23

24.  Polymer– hydroxy propyl methyl cellulose phthalate
 1.5%PEG6000 - plasticizer
 Formulation- sustained release suspension of
theophylline microcapsules
24

25. Heating of
polymer
below its Tg
pressurized at
28mpa for
30sec-5min
temperature
maintained
above tg
25
method of
preparation

26. 26
liquid crystal
system
thermo tropic
lyotropic
nematic
smectic
cholesteric

27.  Lyotropic crystals in invitro condition provide
sustained release.
 Provides thermodynamically , kinetically stable
matrix
 Investigations done using polar lipid-water-peptide
 Released peptide was found out using
immunoreactivity of peptide in plasma
 Peptide is absorbed in pseudo zero order
 Lyotropic LC acts as parenteral depot
 Peptide protected against degradation
27

28.  Ion exchange resins are solid and suitably insoluble high
molecular weight polyelectrolytes that can exchange their
mobile ions of equal charge with the surrounding medium.
 size of the ion-exchange resins -about 20 to about 200 μm
particle sizes.
 Drug – resinate complexes are prepared by batch and column
method Influence of formulation on rate and equilibrium was
done using ion exchange resin.
 Diffusion of drug from resin particles controlled by particle
diffusion process.
28

29.  Coated with SURELEASE(aqueous ethyl cellulose
dispersion)
 pH has no effect on drug release.
 Increase in ionic concentration, increase in rotation
speed will increase the release
 The drug release follows first order kinetics
 Strong acidic cationic exchange resin AMBERLITT
IRP69 ( SR, taste masking, drug stabilizing agent) is
used.
29

30.  The size and state of the particle in the internal phase
play an important role in the final status of the
microparticles.
 The choice of the internal and the external phase of
the emulsion, type of emulsifier and method of
homogenizing two phases will effectively determine
the characteristics of the final microparticles.
 EC is a non-biodegradable and biocompatible and
gastro-resistant polymer which has been extensively
used as drug release retardant which easily forms
microcapsules with a one-step encapsulation method
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31.  Preparation of sustained release microcapsules using
emulsion- solvent evaporation method using EC.
 Preparation has two strategies.
 The first being preparation of o/w emulsion containing
EC dissolved in dichloromethane+ drug as oily phase.
 1.5%SLS in water as aqueous phase. Where oily phase is
added to aqueous phase. 45 min stirring to remove DCM.
And then the microcapsules are obtained.
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32.  The second strategy containing drug and EC as oily phase
in acetone.
 Added to external phase 1.3% tween 80 in 100ml
liq.paraffin.
 Stirred for 5 hrs
 Microcapsules are then obtained
 These are then formulated as suspensions
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33. 33
Pectin +sterile water
Buffered/ non buffered saline is prepared
Both are mixed set aside at 4˚c
Gel is formed

34.  Elderly patients with swallowing dysfunction may benefit
from the oral administration of liquid dosage forms with in
situ gelling properties.
 Gels are made by using METHYL CELLULOSE a thermo
reversible gelation properties containing polymer and
sodium alginate having ion responsive gelation properties
 This is mainly done for ease of administration and provides
suitable integrity for the drug in stomach to produce
sustained release.
 Generally used gelling agents are chitosan, pectin(0.1-2%),
sodium alginate(0.25-1%), methylcellulose(2%),
34

35.  Mixtures of 2.0% methylcellulose and 0.5% alginate
containing 20% d-sorbitol were of suitable viscosity for
ease of swallowing by dysphagic patients and formed
gels at temperatures between ambient and body
temperature allowing administration in liquid form and in
situ gelation in the stomach
 A 2.0% methylcellulose/0.5% alginate formulation
showed improved sustained release compared to that
from 2.0% methylcellulose and 0.5% alginate solutions
and from an aqueous solution of paracetamol
35

36.  Mesogen is the fundamental unit of a liquid crystal that
induces structural order in the crystals.
 Typically, a liquid-crystalline molecule consists of a
rigid moiety and one or more flexible parts.
 The rigid part aligns molecules in one direction, whereas
the flexible parts induce fluidity in the liquid crystal.
 This rigid part is referred to as mesogen, and it plays a
crucial role in the molecule. The optimum balance of
these two parts is essential to form liquid-crystalline
materials.
36

37. 37
Multiple emulsion (w/o/w or o/w/o), Prepared by two step
procedure
First step (o/w)
Primary emulsion
Second step (o/w/o)
Secondary
emulsification phase
37

38. 38
Oil + Aqueous phase Low HLB surfactant + Oil
Blend and heat
up to 70-80º C
Formation of very fine droplets
Heat and blend
with low shear
Oil
Blend with low shear
Multiple emulsion
38

39. Viscosity
 surface tension
conductivity
Syringability
pH
Globule size
Test for sterility
Microscopic method
Particle size distribution
Entrapment efficiency
3
9
Evaluation of Multiple Emulsions

40. Syringability
All the formulation were tested by different size of needle under the
guidance by the experters (Physicians) and the data obtained was put
in tabulated form.
The O/W/O multiple emulsion with a minimum concentration of
surfactants showed excellent syringability. The multiple emulsion
prepared with maximum concentration of surfactants and for given
time period entrapped 83.14 % of Hydroxyprogesterone.
4
0

41. Globule/droplet size determination
Droplet size was determined by the microscopy, the compound
microscope was used to determine the droplet size of the formulation.
It was found that the droplets decrease in size with increase in the
concentration of surfactants. The average diameters of the dispersed
water droplets in o/w/o emulsions
4
1

42. 4
2
Multiple
Emulsion

43. .
Entrapment efficiency
The entrapment efficiency is the capacity of the multiple emulsions
that how much quantity of drug is entrapped in the internal phase. It
was calculated in %.
All the formulations were centrifuged at high speed and the
separated phase was evaluated for drug content.
4
3

44. Sterility Test
All the formulations were subjected for the sterility test by direct
inoculation method (I.P.).
The sterility test was carried out for aerobic and anaerobic
microorganism, fluid thioglycollate media and soybean casein
digest media was used for sterility test. 4
4

45. Stability study
The stability study was carried out of optimized formulation Fa.
Formulation was stored in amber colored ampoule at 40o C for three
months. It was evaluated for physical characteristics.
4
5

46. In -vitro diffusion study
•The drug release profile of all formulations was studied in buffer
media (pH 7.4 and Alcohol 20%) by using K-Cell.
•The cellulose membrane used as a barrier.
•The drug release profile was studied for 24 hrs.
4
6

47. • The amount of the drug diffused out was relatively small,
indicating that the water layer of the multiple emulsion shows a
stable diffusion barrier, thus the drug was released mainly by
permeation through this membrane.
• The comparative drug diffusion studies were carried out,
comparison with the marketed formulation and shown the
percentage drug release of marketed formulation more than the
multiple emulsions.
4
7

48.  Microscopic method
 Dissolution studies
 Entrapment efficiency
 pH
 Viscosity
 surface tension
 Sedimentation volume
 Degree of flocculation
 Ease of dispersibility
48

49.  Liquid crystalline phases are applied for cosmetics
 In treatment of paradontitis the drug is dispersed in gel
such that it adheres to the gum pockets.
 LC of DNCG is applied as mast cell stabilizer used as
prophylactic agent in asthma & hay fever
 Used in treatment of bronchial asthma
49

50. Drug form
Hydroxy progesterone Multiple emulsion
Timolol Liquid eye drops
Theophylline Suspension
Propranolol Hydrochloride Drug resin complex
50

51.  Kenneth J. Fredrick. Performance and problems of
pharmaceutical suspensions, Journal of Pharm. Sciences.
50,531-35,1961
 George M., Grass IV, Robinson J. "Sustained and
controlled release drug delivery systems" ,"Modern
Pharmaceutics" edited by Banker G.S., Rhodes C.T., 2nd
edition, Marcel Dekker, 1990: 639-658pp.
 Longer M.A., Robinson J.R. "Sustained release drug
delivery system" ,"Remington's pharmaceutical sciences"
18th edition, Mack Publishing Company, 1990: 1675-
1684pp.
51

52.  Brahmnkar DM, Jaiswal SB: Biopharmaceutics and
Pharmacokinetics – A Treatise. 1sted. Delhi: Vallabh
Prakashan; 1995. p. 62, 282.
 Liberman HA, Martin A, Gilbert R,. Banker S:
Pharmaceutical Dosage Forms: Disperse system: Marcel
Dekkar. Volume III; 1994; p. 423-471.
 Liberman HA, Martin R, Gilbert R, Banker S:
Pharmaceutical Dosage Forms: Disperse system: Marcel
Dekkar. Volume II,;1994; p. 47- 97, 261 – 310, 183- 239.
 Liberman HA, Martin R, Gilbert R, Banker S:
Pharmaceutical Dosage Forms: Disperse system: Marcel
Dekkar. Volume III; 1994; p. 423-471.

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