Download annexure – ii - Rajiv Gandhi University of Health Sciences

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
NAME OF THE CANDIDATE NAYAZ AHMED
S/O PSA Bashu Saheb,
AND ADDRESS:
Door no: 216,144(new).Elahi Manzil,
2nd Cross Road, Behind Rajasthan Oil Mill,
Reddy Layout, Bowrilalpet, Robertsonpet,
Kolar Gold Field, Karnataka.563122.
Email: [email protected]
2.
NAME OF THE INSTITUTE:
Krupanidhi College of Pharmacy,
Chikka Bellandur,
Carmelaram Post,
Varthur Hobli,
Bangalore – 560035.
3.
COURSE OF THE STUDY & Master of Pharmacy
SUBJECT:
(Pharmaceutics)
4.
DATE OF ADMISSION TO July 6th 2010
THE COURSE:
5.
TITLE OF THE TOPIC:
SOLUBILITY ENHANCED CIPROFLOXACIN FORMULATION AND
ITS EVALUATION
OF SELENO-QUIANAZOLONE AND EVALU
6.
BRIEF STUDY OF THE INTENDED WORK:
6.1 Need of Study:
A number of new active compounds show a very low solubility in biological
media due to lipophilic nature. The most pharmaceutical industries are facing a
major challenge to increase the solubility by using different formulation technique to
reach an acceptable bioavailability. The ability of surfactants to enhance the
solubility of poorly water-soluble compounds in an aqueous solution is widely
known and used in many aspects of drug formulation development. Surfactants are
used as wetting agents to improve tablet dissolution and are commonly used in the
media for dissolution testing to maintain sink conditions for the drug1.
Ciprofloxacin is the most potent first generation fluoroquinolone active
against a broad range of bacteria, the most susceptible ones are the aerobic gram
negative bacilli2. The Minimal Inhibitory Concentration against these bacteria is
usually < 0.1µ mL-1. it has oral efficacy and good tolerability. It is used in urinary
tract infections, gonorrhea, chancroid , bacterial gastroenteritis, typhoid, respiratory
infections etc. It is rapidly absorbed orally, but food delays absorbtion and first pass
metabolism occurs. It has an oral bioavailability of 60-80% and elimination half life
of 3-5 hours. It has an high penetrability but low aqueous levels due to its very low
aqueous solubility and poor dissolution can cause formulation problems and limit its
therapeutic application by delaying the rate of absorption and the onset of action2.
The solubility of the ciprofloxacin can be enhanced by using surfactants.
The enhancement of aqueous solubility by surfactants occurs as a result of the dual
nature of the surfactant molecule. Surfactants typically contain discrete hydrophobic
and hydrophilic regions, which allow them to orient at polar–non polar interfaces,
such as water/air interfaces. Once the interface is saturated, the surfactants selfassociate to form micelles and other aggregates, whereby their hydrophobic regions
are minimized and shielded from aqueous contact by their hydrophilic regions. This
creates a discrete hydrophobic environment suitable for solubilisation of many
hydrophobic compounds1.
Objective of the study :
The primary goal of this investigation would be to formulate and
evaluate poorly water soluble drug ciprofloxacin for enhancing its solubility by
using surfactants in the formulation.
The individual objectives to be achieved include:
1) Enhancement of solubility.
2) Enhancement of absorption.
3) Improvement of stability.
Review of Literature:
Modi A, Tayade P studied comparative solubility enhancement profile of
valdecoxib with different solubilization approaches . This method is commonly
known as micellar solubilization since they form micelles, which are association
aggregates of surfactant molecule. Different types of surfactants viz. cationic,
anionic and Non-ionic were studied for improvement of solubility of valdecoxib. A
number of non-ionic surfactants were studied since non-ionic surfactants are more
tolerable and compatible with biological system than ionic surfactants. All
surfactants exhibit significant improvement of aqueous solubility of Valdecoxib. The
solubility of drug increased with increasing surfactant concentration linearly3.
Yadav VB, Yadav AV studied enhancement of solubility and dissolution rate
of BCS class ll pharmaceuticals by using Nonaquious Granulation Technique.
Liquisolid and Compaction granulation technique has been proved to be a imperative
development to increase the solubility, dissolution rate and other physicochemical
characteristics of fenofibrate (FF), griseofulvin (GF) and Lemotrazine(LT)which are
very slightly water soluble using PEG-400 as hydrophilic binder, silca as
absorbent/coating material, microcrystalline cellulose and sodium starch glycolate as
excipients in granulation technique4.
Bandela JJ, Anupama CH presented Advanced PEGylation for the
development of raloxifene hydrochloride, BCS class II drug by using solvent
evaporation technique and it was found that the PEG conjugates of raloxifene HCl
are useful to enhance the dissolution rate of raloxifene HCl, a poorly water-soluble
drug5.
Sharma D, Soni M, Kumar S, GD Gupta studied various methods to
enhance the solubility of BCS class ll drug and conclusion was Solid dispersions are
one of the most attractive processes to improve drug’s poor water solubility. Various
solubility enhancers like water-soluble carriers, co solvents, surfactants and
superdisintegrants via solid dispersion approach (fusion method and solvent
evaporation method) aids in solubility enhancement.
These significantly help to improve the bioavailability and bioequivalence6.
Chaudhari P, Sharma P, Barhate N, Kulkarni P, Mistry C studied the
Solubility enhancement of hydrophobic drugs using synergistically interacting
cyclodextrins and cosolvent and suggested that the increase in valdecoxib solubility
was due to synergistic effect in the presence of CDs and PEG-400, as well as
increase in CD complexation efficiency. Addition of PEG-400, poloxamer-188 and
CDs increased the solubility of the model drug from 0.01 mg/ml in distilled water.
However, addition of poloxamer- 188 made the system more complex and hampered
the synergistic effect at higher concentrations. The study describes the increase in
solubility produced by cosolvents as well as the increase in solubility produced at all
CD concentrations. Thus it provides the dynamics of the combined cosolvent–CD
technique in solubilisation of non-polar drugs7.
Ahire BR, Rane BR, Bakliwal SR, Pawar SP studied Solubility
Enhancement of Poorly Water Soluble Drug by Solid Dispersion Techniques and
found the Formulation Kneading method 1:2 (KM 1:2) showed an exceptional
increase in solubility of Nevirapine as compared to other Formulations. It was
observed that an increase in solubility of about 1.7 and 1.8 fold with (KM 1:2) as
compared to the drug alone in distilled water and pH 6.8. Solubility studies clearly
indicated Kneading method of preparing solid dispersions is the method which
enhances the solubility greatly as compared to physical mixing and
Solvent evaporation because of synergistic effect of trituration and solubilization of
used solvent leading to improvement in solubility8.
Nagabhushanam MV studied formulation studies on cyclodextrin complexes
of meloxicam and found that Among the two cyclodextrins, that is-Cyclodextrin
(-CD) and HP--Cyclodextrin (HP--CD), CD complexes were found to be more
suitable for tablet formulation by both direct compression and wet granulation
methods. Thus, cyclodextrin complexation employing kneading method is
recommended as an effective and efficient technique for enhancing the dissolution
rate, dissolution efficiency of meloxicam9.
Varanda F et al studied Solubility of Antibiotics in Different Solvents.
Hydrochloride Forms of Tetracycline, Moxifloxacin, and Ciprofloxacin The
solubilities of tetracycline hydrochloride, moxifloxacin hydrochloride, and
ciprofloxacin hydrochloride were measured in several solvents, such as water,
ethanol, 2-propanol, and acetone, in the temperature range of 293.15-323.15 K for
ciprofloxacin.HCl and moxifloxacin.HCl and 288.15-310.15 K for tetracycline. All
the antibiotics have the same solubility order; that is, they are more soluble in water
than in ethanol, and more soluble in ethanol than in 2-propanol and acetone10.
Dash S, Nath LK, Bhise S, Bhuyan N studied Aqueous solubility of
ciprofloxacin in the presence of metal cations and result was The solubility of
ciprofloxacin in 0.05M H2SO4 at 37.0 ± 0.2°C was 46.65 mgml-1 (0.12M). Except
for magnesium sulphate, all the cations investigated progressively increased the
aqueous solubility of ciprofloxacin. Ferrous ion had the greatest increase. It was
followed by ferric, calcium and aluminium ions. Potassium and sodium ions had
very slight increase in ciprofloxacin solubility.
As the amount of magnesium sulphate increased, the aqueous solubility of
ciprofloxacin increased slightly initially but then decreased progressively11.
Kumar S, Prabha SK, Sathish K, Satyanarayan K, Kumar RH studied
solubility enhancement of a drug by liquisolid technique. In this Liquisolid technique
gives a design to enhance the absorption as well as dissolution rate their by it may
enhance the bio availability of a poorly soluble, insoluble or lipophilic drug and to
formulate them into immediate release or else sustain release by selection of suitable
solvent and carrier.
In this technique drug is dissolved in a non volatile solvent and their by
this liquid medicament is converted to non adherent, dry looking and free flowing by
using suitable carrier and coating material. Because of the presence of drug in the
state of solubilised or moleculary dispersed state, so solubility of insoluble drug is
enhanced12.
Deshmukh DB, Gaikwad PD, Bankar VH, Pawar SP studied Dissolution
Enhancement of Poorly Water Soluble Diacerein by Solid Dispersion Technique in
presence of PVP K-30 and HPMC classified as AL type. The study shows that the
dissolution rate of Diacerein can be enhanced to a great extent by solid dispersion
technique using solvent evaporation method due to wetting and solubilisation
phenomenon13.
Viral S, Dhiren P, Mane S, Umesh U studied Solubility and Dissolution
Rate Enhancement of Licofelone by Using Modified Guar Gum The results of
present investigation indicated that co-grinding mixture of licofelone with modified
guar gum could be useful in developing an oral dosage form with increased
solubility and hence improved dissolution and oral bioavailability of poorly water
soluble drug14.
Kamalakkannan V, Puratchikody A, Masilamani K, Senthilnathan B
Studied solubility enhancement of poorly soluble drugs by solid dispersion technique
and concluded that Solid dispersions can increase dissolution rate of drugs with
poor water-solubility but stability of these systems needs consideration and the
carriers need to be selected for drugs on a case by case basis. Solvent systems
consisting of mixtures of solvents can be used to optimize concentration in solution
processing parameters influence the type of glass amorphous system formed15.
Ahmed MA, Rhgigh AM, Shakeel F Studied effect of surfactants on the
crystal properties and dissolution behaviour of aspirin The effect of surfactant
concentration on melting point, true density, bulk density, crystal porosity and
solubility of aspirin crystals were examined.
The dissolution profiles of tablets prepared with different concentration of
SLS were significantly different from control aspirin tablets. The best drug release
(97 %) was obtained in 120 min with 0.1 M concentration of SLS. Overall SLS was
found to be the best surfactant for the preparation of aspirin tablets16.
Seedher N ,Agarwal P Studied various solvent systems for solubility
enhancement of enrofloxacin and found that aqueous solubility of enrofloxacin could
be increased up to 26 times. Co-solvents alone produced only small increase in
solubility. However, the combined effect of co-solvents and buffer was synergistic
and a large increase in solubility could be attained. Ionic surfactants were found to
be much better solubilizing agents than non-ionic surfactant. Amongst ionic
surfactants, solubility was found to be very high in anionic surfactant, sodium
dodecylsulphate as compared to the cationic surfactant, cetyltrimethylammonium
bromide17.
7.
Materials & Methods:
7.1 Source of Data:
Data will be obtained from the literature search and experimental work,
which includes preformulation studies, formulation, product evaluation, optimization
and subjecting the formulation to accelerated stability studies.
Data on drugs
will
be collected from
drug information centre,
physicochemical data base and literature search.
7.2 Method of Collection of Data (including sampling procedure, if any):
The physicochemical properties, of the drug will be collected from drug
information center, various standard Books, journals, websites and other sources like
research literature bases data such as Medline, Science Direct etc.
The experimental data will be collected from study of the drug; its formulation,
through investigation of the process and product variables in the laboratory of
Krupanidhi College of Pharmacy, Bangalore-35.
The steps involved in the methodology are:
1. Selection of the excipients and surfactant
2. Pre-formulation studies
3. Conducting phase solubility studies to determine the solubility.
4. Formulation by wet granulation technique
5. Evaluation of the formulation e.g. weight variation, friability etc
6. In vitro drug release studies
7. Stability studies under ICH guide lines.
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:
N/A
7.4 Has the Ethical Clearance been obtained from your Institution in case of 7.3?
N/A
8.
LIST OF REFERENCES:
1. Liu R. Water insoluble drug formulation. 2nd ed. Boca raton: CRC Press
Taylor and Francis Group; 2008. p.271.
2. Tripathi KD. Essentials of medical pharmacology. 6th ed. New Delhi:
Jaypee Brothers Medical Publishers (P) Ltd; 2008.p. 688-90.
3. Modi A, Tayade P. A comparative solubility enhancement profile of
valdecoxib with different solubilization approaches. Ind J Pharm Sci 2010
Nov 30;69:274-8.
4. Yadav VB, Yadav AV. Enhancement of solubility and dissolution rate of
BCS class ll pharmaceuticals by using non-aqueous granulation technique.
liquisolid and compaction granulation. Int J Pharm Res Dev 2008
Feb;1(12):1-12.
5. Bandela JJ, Anupama CH. Advanced pegylation for the development of
raloxifene hydrochloride, BCS class II drug. J Young Pharm 2009;1:295300.
6 . Sharma D, Soni M, Kumar S, GD Gupta. Various methods to enhance the
solubility of BCS class ll drug. Res J Pharm Technol 2009 AprJun;2(2).220-4.
7 . Chaudhari P, Sharma P, Barhate N, Kulkarni P, Mistry C. Solubility
enhancement of hydrophobic drugs using synergistically interacting
cyclodextrins and cosolvent. Curr Sci 2007 jun 10;92(11):1586-91.
8 . Ahire BR, Rane BR, Bakliwal SR, Pawar SP. Solubility enhancement of
poorly water soluble drug by solid dispersion techniques. International
Journal of PharmTech Research 2010July-Sept;2(3); 2007-15.
9 . Nagabhushanam MV. Formulation studies on cyclodextrin complexes of
meloxicam. Int J Pharm Technol 2010 Mar;2(1); 89-102.
10. Varanda F, Maria JPM, Ana IC, Dohrn R, Makrydaki FA, Voutsas E et
al. Solubility of antibiotics in different solvents hydrochloride forms of
tetracycline ,moxifloxacin, and ciprofloxacin. Ind Eng Chem Res 2006;
45(18):6368-74.
11. Dash S, Nath LK, Bhise S, Bhuyan N. Aqueous solubility of ciprofloxacin
in the presence of metal cations. Trop J Pharm Res 2005; 4(1): 349-54.
12. Kumar S, Prabha SK, Sathish K, Satyanarayan K, Kumar RH. Solubility
enhancement of a drug by liquisolid technique. Int J Pharm Bio Sci 2010
sep-jul;1(3):1-5.
13. Deshmukh DB, Gaikwad PD, Bankar VH, Pawar SP. Dissolution
enhancement of poorly water soluble diacerein by solid dispersion
technique. J Pharm Sci Res 2010; 2 (11): 734-9.
14. Viral S, Dhiren P, Mane S, Umesh U. Solubility and dissolution rate
enhancement of licofelone by using modified guar gum. Int J Pharm
Technol Res 2010 Jul-Sep;2(3):1847-54.
15. Kamalakkannan V, Puratchikody A, Masilamani K, Senthilnathan B.
Solubility enhancement of poorly soluble drugs by solid dispersion
technique. J Pharm Res 2010; 3(9):2314-21.
16. Ahmed MA, Rhgigh AM, Shakeel F. Effect of surfactants on the crystal
properties and dissolution behavior of aspirin. Asian Journal of Research
in Chemistry 2009 Jul-Sep;2(2):202-6.
17. Seedher N ,Agarwal P. Various solvent systems for solubility enhancement
of enrofloxacin. Indian J Pharm Sci 2009 Jan–Feb; 71(1): 82–87.
9.
Signature of the candidate:
(NAYAZ AHMED)
(((Rajesh
10.
Remarks of the Guide:
Pharmacokinetic profile of drug has direct bearing on clinical performance.
Formulation strategy to alter it, is important breakthrough in improving clinical
efficacy. This work is an effort in this direction for a widely used molecule. The
protocol may be approved.
11.
Name & Designation (in BLOCK LETTERS)
11.1 Guide
Prof. Dr.R.S THAKUR
PROFESSOR AND HEAD
Department of Pharmaceutics
Krupanidhi College of Pharmacy
Bangalore – 560035
11.2 Signature of guide
11.3 Head of the Department
Prof. Dr.R.S THAKUR
PROFESSOR AND HEAD
Department of Pharmaceutics
Krupanidhi College of Pharmacy
Bangalore – 560035.
11.4 Signature of HOD:
12.
12.1 Remarks of the Principal:
The program and the that Mr. Rajesh
12.2 Signature of the Principal
Prof. Dr. N. PREMKUMAR
Principal
Krupanidhi College of Pharmacy,
Chikka Bellandur,
Carmelaram Post,
Varthur Hobli,
Bangalore – 560035.