Download Oral suspension

6. BREIF RESUME OF THE INTENDED WORK:
6.1 Need for study:
Helminthes infections are the most common infections, which affects the large proportions of the world’s
population. In the treatment of parasitic diseases, the anti-helmintics drugs are used indiscriminately.
About half of the world’s population suffers from Helminthiasis and the number is increasing day by day. It
is not only limited to tropical and subtropical countries but is also to endemic in many regions because of
poor sanitation, poor family hygiene, malnutrition and crowded living condition. There is an urgent need to
apply powerful approaches to formulate a successful anthelmintic dosage forms1&2. The drug used for
helminthes worm infections are niclosamide, piperazine, benzimidazoles, pyrantel, levamisole, ivermectin,
praziquantel, emodepside and closantel etc.
Levamisole, is an anthelminthic and immunomodulator and a more potent levo-rotatory isomer, Hence the
name given levamisole. Levamisole has been used in humans to treat parasitic worm infections. For
Ascariasis adult: 150 mg as a single dose. Child: 3 mg/kg as a single dose. For Ancylostomiasis adult: 2.5
mg/kg as a single dose, Child: 2.5 mg/kg as a single dose. For mixed ascariasis hookworm infections adult:
2.5 mg/kg as a single dose. Child: 2.5 mg/kg as a single dose. The dose of veterinary usage is 20mg/kg for
dogs, monkeys, rats14. It works by paralysing susceptible intestinal worms which are then excreted from
the intestines. Levamisole also enhances cellular immune responses in humans. This is well-absorbed from
the GI tract. Peak plasma concentrations are achieved in 1.5-2 hours. It metabolise extensively in the liver.
Excretion occur mainly in the urine 70% as metabolites and 5% as unchanged drug and small amounts in
the faeces.
A Pharmaceutical suspension is a coarse dispersion in which internal phase is dispersed uniformly
throughout the external phase. The internal phase consisting of insoluble solid particles having a specific
range of size which is maintained uniformly throughout the suspending vehicle with aid of single or
combination of suspending agent. The external phase suspending medium is generally aqueous in some
instance, may be an organic or oily liquid for non oral use. The various advantages of the suspension are
they improve chemical stability of certain drug, drug in suspension exhibits higher rate of bioavailability
than other dosage forms, bioavailability is in following order Solution > Suspension > Capsule >
Compressed Tablet > Coated tablet, Duration and onset of action can be controlled and suspension can
mask the unpleasant/ bitter taste of drug13.
Classification of suspensions
1. Based on General Classes
Oral suspension
Externally applied suspension
Parenteral suspension
2. Based on Proportion of Solid Particles
Dilute suspension (2 to10%w/v solid)
Concentrated suspension (50%w/v solid)
3. Based on Electro kinetic Nature of Solid Particles
Flocculated suspension
Deflocculated suspension
4. Based on Size of Solid Particles
Colloidal suspension (< 1 micron)
Coarse suspension (>1 micron)
Nano suspension (10 ng)13
Features Desired In Pharmaceutical Suspensions:
 The suspended particles should not settle rapidly and sediment produced, must be easily re-suspended
by the use of moderate amount of shaking.
 It should be easy to pour yet not watery and no grittiness.
 It should have pleasing odour, colour and palatability.
 Good syringeability.
 It should be physically, chemically and microbiologically stable.
6.2Review of Literature :
 This comprehensive review briefly describes the history and pharmacology of albendazole as an
anthelmintic drug and presents detailed summaries of the efficacy and safety. The incidence of
side effects reported in the published literature is very low, with only gastrointestinal side effects
occurring with an overall frequency of just >1%. Albendazole's unique broad-spectrum activity is
exemplified in the overall cure rates calculated from studies employing the recommended doses for
hookworm (78% in 68 studies: 92% for A. duodenale in 23 studies and 75% for N. americanus in 30
studies), A.lumbricoides (95% in 64 studies), T. trichiura (48% in 57 studies), E. vermicularis (98%
in 27 studies), S. stercoralis (62% in 19 studies), H. nana (68% in 11 studies), and Taenia spp. (85%
in 7 studies). The facts that albendazole is safe and easy to administer, both in treatment of
individuals and in treatment of whole communities where it has been given by paramedical and
nonmedical personnel, have enabled its use to improve general community health, including the
improved nutrition and development of children6.
 This review briefly describes the solid lipid nanoparticle suspension enhanced the therapeutic
efficacy of praziquantel against tape worm. PZQ-loaded hydrogenated castor oil solid lipid
nanoparticle (PZQ-HCO-SLN) suspension was prepared by a hot homogenization and
ultrasonication method. Results demonstrate that the PZQ-HCO-SLN suspension is a promising
formulation to enhance the therapeutic efficacy of PZQ7.

This review briefly describes the anthelmintic Potential of Mimusops elengi Linn. The aim of present
study was to evaluate anthelmintic potential of crude extract and it’s fractions of the leaves of the
plant Mimusops elengi(linn.),sapotaceae.The methanolic extract and it’s fractions were used for the
bioassay by using adult Indian earthworms pheretima posthuma.The results indicated that the
methanolic extract and ethylacetate fraction of the leaves exhibited significant anthelmintic activity
with respect to standard and control. Albendazole was included as standard reference and distilled
water as control. The paralysis and death of the worms was significantly determined at high
concentrations of methanolic extract and it’s ethyl acetate fraction.10
 This reviews the prevalence of soil-transmitted helminthic infections in Nigeria and current control
efforts. Intestinal helminth infections (Ascaris, Trichuris and hookworm) in Nigeria remain as
prevalent as they were in the 1970s. Majority of those affected are young children between the
ages of 5 and 14 years living in rural areas and urban slums. Cultural, socio-economic and
environmental factors are major contributors to the persistence of these infections. Although the
World Health Organization (WHO) recommends chemotherapy for Ascaris, Trichuris and hook
worm infections targeted at school-age children as a feasible and cost-effective control strategy,
there is no policy-backed approach for helminth control in Nigeria. This paper makes a case for
regular school-based programs to deliver chemotherapy so as to reduce the burden of helminth
infection in school age children in Nigeria11.
 This review briefly describes the efficacy of two netobimin oral suspensions (5% and15%) in sheep
naturally infected with Dicrocoelium dendriticum. This study was carried out to compare the
efficacy of two suspensions (5% and 15%) of netobimin against Dicrocoelium dendriticum in
naturally infected sheep. Fifteen Merino sheep, 4 to 7 years old, were used in this survey. Animals
were divided into three equal groups each of five sheep on the basis of bodyweights and D.
dendriticum egg counts in per gram faeces. Group A and group B sheep were treated orally with 5%
and 15% suspension of netobimin, respectively; both at a dose rate of 20 mg kg−1. Group C sheep
were left untreated as controls. Twenty-one days post-treatment all sheep were slaughtered for
post-mortem examination. All D. dendriticum from the liver and gall bladder were recovered and
counted. The results showed that the efficacy of 5% and 15% suspension of netobimin was 90.80%
and 91.50%, respectively, and the use of 15% suspension in sheep is discussed.3
 This reviews anthelmintic effect of febantel on various species of gastrointestinal nematodes.
Febantel in a 2.5% suspension was given to 99 sheep naturally infected with intestinal nematodes
(mainly Trichostrongylus, Ostertagia, Cooperia, Haemonchus, Bunostomum and Nematodirus),
from a flock of 209 in Spain (Aragon). A dose of 5 mg/kg was given to 46 sheep and 10 mg/kg to 49
sheep. Eight days later faecal examinations revealed that 43(93.5%) and 47 (95.9%) were free from
parasites. In the remaining five animals, numbers of larvae/g of faeces fell from 600-700 to less
than 30. Four infected sheep given 25 mg/kg febantel were all parasite-free at PM examination. The
preparation was well tolerated and there were no abortions or teratogenic effects4.
 This review briefly describes the efficacy of closantel plus albendazole liquid suspension against
natural infection of gastrointestinal parasites in camels. Oral administration of closantel in a dose of
10 mg/kg plus albendazole in a dose of 5 mg/kg liquid suspension was studied in 75 camels
naturally infected with various types of gastrointestinal parasites. The camels involved were 15
pregnant she-camels, 20 non-pregnant she-camels and 40 male camels of various ages. Each camel
received a single oral dose of closantel (10 mg/kg) plus albendazole (5 mg/kg) orally. Two weeks
later, 20 camels of this group were re-dosed again with the same dose of the anthelmintic. Fecal
egg counts and generic determination of third stage larvae was performed. Results indicated that
six different species of gastrointestinal tract parasites were identified in camels. Single treatment of
closantel plus albendazole mixture reduced egg counts in camels by 100%, 100%, 98% and 77%
for Haemonchus longistipes, Ascaris spp., Monezia expansa and Fasciola hepatica, respectively.
However, administration of the drug twice on the base of 2 weeks apart significantly raised the
efficacy of the drug for clearance of the parasites from 92.5% to 100% in camels infected with
various parasites. Camels were not adversely affected by treatment5.
 This reviews effectiveness of Various Anthelmintics in the Treatment of Moniliformiasis. Humans
particularly become infected with Moniliformis moniliformis. The effectiveness of pyrantel
pamoate, ivermectin, praziquantel, niclosamide, thiabendazole, and mebendazole was evaluated in
the treatment of moniliformiasis in laboratory-infected female Wistar rats. The most effective drug
in the treatment of moniliformiasis in rats was mebendazole, two doses resulted in a 69% reduction
in worm burden after 2 weeks; however, 50% of the rats receiving the treatment died within 2
weeks after first administration of the drug. Two surviving rats that had been treated with
mebendazole exhibited evidence of hepatic dysfunction characterized by extremely elevated levels
of alkaline phosphatase in conjuction with depressed serum albumin levels. It is hypothesized
that Mo. moniliformis may metabolize the drug and release a metabolite that is highly toxic to the
host. On the basis of these data, thiabendazole is recommended as the drug of choice for the
treatment of human acanthocephaliasis until more extensive testing can be conducted 8.
 This reviews mebendazole/trichlorfon combination. a new anthelmintic for removing monogenetic
trematodes from fish. Mebendazole effectively removed G. elegans after a 24-h. exposure to 0·01
mg l-1, but it had no effect on D. vastator up to 2·0 mg l-1. Trichlorfon was 95% effective on D.
vastator between 0·4 and 1·6 mg l-1 after a 24-h exposure, but it had no effect on G. elegans up to
2·0 mg l-1. A combination of mebendazole at 0·4 mg l-1 and trichlorfon at 1·8mgl-1 was 100%
effective on both parasites. The minimum effective exposure time was 24 h and shorter exposure
times, even at high dose levels, were not effective. The combination had no apparent toxic effect
on fish, except possibly catfish, and field tests in various geographical areas of the United States
showed that the combination was effective in all cases9.
6.3 Objectives of the study:
The aim of the research work is formulation and evaluation of oral suspensions containing an anthelmintic
drug (levamisole). The objectives are as follows:
1. Pre formulation studies for selection of suitable excipients to develop the dosage form based on
physicochemical properties of drug and excipients.
2. Screening of excipients for compatibility and efficacy for developing the formulation.
3. Carry out pre formulation study of levamisole drug.
4. Preparation of oral suspensions.
5. Evaluation of oral suspensions, in vitro
6. Optimize the formulation using experimental design technique regarding particle size, particle size
distribution, crystallinity, zeta potential, stability and release profile etc.
7. Evaluation of formulated product and identification of defects.
8. Study the stability of the optimized formulation following ICH guidelines.
The various components, which are used in suspension formulation, are as follows: 12
Components
Functions
API
Active drug substances
Wetting
agents
They are added to disperse solids in continuous liquid phase.
Flocculating
agents
They are added to floc the drug particles
Thickeners
They are added to increase the viscosity of suspension.
Buffers
and pH adjusting agents
They are added to stabilize the suspension to a desired pH range.
Osmotic
agents
They are added to adjust osmotic pressure comparable to
Coloring
agents
They are added to impart desired color to suspension and
Preservatives
They are added to prevent microbial growth.
External
liquid vehicle
They are added to construct structure of the final suspension.
biological fluid.
Improve drug elegance.
7.1 Source of Data :
Data will be obtained from
- Internet facilities.
-Indian genomix company research articles
-Literatures and related articles from library of krupanidhi college of pharmacy.
-Indian institute of science and other research publications.
-Drug information center (Banglore) and current index of medical specialties.
7.2 Matereials and method of collection of data (including sampling procedures if any):
The drug and the excipients will be procured from the industry and Krupanidhi College of Pharmacy. All
the reagents to be used will be of analytical grade.
The drugs related to
physicochemical, physiological and pharmacological details of drug will be
collected from drug information center, standard books, and research literature database such as Medline,
science direct etc.
Experimental data will be collected from the evaluation and designed formulation and then subjecting
the formulation to different studies, wetting of the particles, sedimentation, particle size, electrokinetic
properties.
7.3 Does the study require any investigations or interventions to be conducted on patients or other human
or animals ? If so please describe briefly.
-----NO----7.4 Has the Ethical Clearance been obtained from your Institution in case of 7.3?
----NOT APPLICABLE---8.LIST OF REFERENCES :
1. Gilleard JS. Understanding anthelmintic resistant. International journal parasitology 2006; 36(12):
1227-1239.
2. Piyush yadav, rupali singh. A review on anthelmintic drugs and their future scope. International
journal of pharmacy and pharmaceutical science 2011; 3(3):17-21.
3. Senlik B, cirak VY, tinar R. Performed efficacy of two netobimin oral suspensions. Small ruminant
research; 80(1): 104-106.
4. Sanchez acedo, Gutierrez galindo J, Castillo Hernandez JA. Anthelmintic effect of febantel on
various species of gastrointestinal nematodes. Veterinar- medizinische nachrichten 1980:35-43
5. Al-qudah KM, sharif LA, al-rawashden OF. Efficacy of closantel plus albendazole liquid suspension
against natural infection of gastrointestinal parasites. Vetparasitol 1999: 82(2):173-178.
6. Horton J. A review of anthelmintic efficacy and safety. Parasitology2000; 121sppl:113-132.
7.
Shuyu xie et al., Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of
praziquantel. Int j nano medicine 2011; 6:2367-2374.
8. Dennis J, Richardson and Cheryl d brink. Effectiveness of various anthelmintics in the treatment of
Moniliformiasis 2011: 11(8):1151-1156.
9. Beverly A goven, Donald F amend. Mebendazole/trichlorfon combination. Journal of fish biology;
20(4):373-378.
10. Goutam kumar jana et al., evaluation of anthelmintic Potential of Mimusops elengi Linn. Journal of
pharmacy research article 2010: 10(3):2514-2515.
11. Olaniyi J Ekundayo, Muktar H Aliyu, Pauline E Jolly. A review of intestinal helminthiasis in Nigeria
and the need for school-based intervention. Journal of rural and tropical public health 6, 2007:3339.
12. Cooper & Gun. Sixth edition. “Dispersed system” tutorial Pharmacy: p.75-78.
13. Dr. Mukesh Gohel et al., Pharmaceutical suspensions review. available from: URL:
http://www.pharmainfo.net/free-books/pharmaceutical-suspensionsa-review
14. Koyama K, Oishi T, Ishii A, Deguchi T. Metabolic fate of levamisole in rats, dogs and
monkeys1983. Oyo Yakuri26:869-876.