IMPROVED BIOAVAILABILITY OF VALSARTAN: A NOVEL ORAL FILM DELIVERY SYSTEM

Abstract

The present invention provides a hypertension treating Valsartan oral disintegrating film and a preparation method thereof. The fast dissolving thin oral film containing Valsartan, comprising Valsartan and pharmaceutically acceptable excipients; wherein the weight of Valsartan 40w/w, Hydroxypropyl Methylcellulose E5 ranges from 40w/w to 160w/w, Polyethylene Glycol 400 ranges from 50w/w to 100w/w, Dimethyl sulfoxide 5w/w, Crospovidone 20w/w and Ethanol quantity sufficient; wherein the fast disintegrating thin oral film contains physical appearance as smooth, weight 275mg, drug content 40.11mg/film, Thickness 0.034mm, Folding endurance 101, dispersion test passed, wherein the fast disintegrating film prepared by using HPMC E5 at 1:3 ratio shows better drug release up to 98.11% within 5 mins. The films are prepared by solvent casting method, comprising: dissolving HPMC E5 in alcoholic solution; dissolving Valsartan, Crospovidone, Dimethyl sulfoxide, and PEG 400; casting the solution and curing under an infrared lamp; and trimming dried thin films. The thin oral film may be useful as a potential medication agent for the treatment of hypertension and heart insufficiency. The fast disintegrating thin oral film can achieve rapid dissolution and rapid drug efficacy in the oral cavity and can provide an enhanced bioavailability and a quick dissolving novel oral film drug delivery system.

Specification

Description:FIELD OF THE INVENTION
This invention relates to a fast disintegrating thin oral film comtaining Valsartan and process for preparing the same. The oral film formulation according to the present invention can achieve rapid dissolution and rapid drug efficacy in the oral cavity. The oral film formulation of Valsartan may be used for the treatment of hypertension and heart failure.
BACK GROUND OF THE INVENTION
Hypertension is a most common cardiovascular disease in the society. The life style of people's living and the increased load of work increasing the number of people suffering from hypertension. The incidences of hypertension are increasing significantly and can cause damage to other body organs also such as the heart, brain, and kidneys etc. Valsartan is a highly effective antihypertensive drug developed with a chemical name of N-pentanoyl-N-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-L-valine, is a non-peptide angiotensin II (ATII) receptor antagonist. It is useful for hypertension, stable blood pressure reduction, strong efficacy, long duration of action, and good patient tolerance. The antihypertensive activity of the Valsartan with the pharmaceutically acceptable excipients may also be manifested in the hypertensive state or high blood pressure situation. The Valsartan compound with the pharmaceutically acceptable excipients can therefore be used as pharmaceutical active ingredients in antihypertensives medicaments for the treatment of high blood pressure and cardiac dysfunction. The patient treatment using oral tablets with higher dose and longer durations are difficult to provide to children, elderly patients, as they cannot swallow tablets or capsules. In addition, drinking water availability for certain patients at the time of drug administration may be difficult. Thin films are easy to carry and take, and is particularly suitable for patients with dysphagia. Therefore, chemists are designing oral disintegrating film formulation containing a therapeutically effective amount of Valsartan and capable of rapidly disintegrating in the mouth[Balakrishna, T., 2022. Development and Evaluation of Valsartan Fast Disintegrating Films. Asian Journal of Pharmaceutics (AJP), 16(1); CN108403668(B) discusses valsartan orally disintegrating film for treating hypertension contains valsartan and a film-forming material, wherein the film-forming material is a combination of pullulan and polyvinyl alcohol, and the weight ratio of pullulan to polyvinyl alcohol is (1-5):(1-5)]. The orally disintegrating film formulation provides convenient administration of drug without the use of drinking water. The present invention develops a Valsartan-containing orally disintegrating film so that the entire amount of Valsartan is released from the formulation at an early stage. The characteristics of the orally disintegrating film formulation is that it is rapidly dissolving in the oral cavity and initiates rapid onset of drug effect on the patient.
OBJECTS OF THE INVENTION
The main object of the present invention is to provide a fast dissolving thin oral film comprising Valsartan.
Still another object of the present invention is to provide a process for the preparation of fast dissolving thin oral film comprising Valsartan.
Another object of the present invention is to provide an oral disintegration-type film formulation for rapid dissolution and rapid drug efficacy in the oral cavity.
Yet another object of the present invention is to provide a fast dissolving thin oral film comprising Valsartan useful as a potential medications agent for the treatment of high blood pressure and cardiac ailments.
SUMMARY OF THE INVENTION
The present invention provides a fast disintegrating thin oral film containing Valsartan and pharmaceutically acceptable excipients. Accordingly, in an embodiment, the present invention provides a fast disintegrating thin oral film containing Valsartan wherein the pharmaceutically acceptable excipients are Hydroxypropyl Methylcellulose E5, Polyethylene Glycol 400, Dimethyl sulfoxide, Crospovidone and Ethanol. Accordingly, in an embodiment, the present invention provides a fast disintegrating thin oral film containing Valsartan wherein the weight of Valsartan 40w/w, Hydroxypropyl Methylcellulose E5 ranges from 40w/w to 160w/w, Polyethylene Glycol 400 ranges from 50w/w to 100w/w, Dimethyl sulfoxide 5w/w, Crospovidone 20w/w and Ethanol quantity sufficient. In an embodiment the present invention provides a fast disintegrating thin oral film containing Valsartan wherein the fast disintegrating thin oral film contains physical appearance as smooth, weight 275mg, drug content 40.11mg/film, Thickness 0.034mm, Folding endurance 101, dispersion test passed. The present invention provides a method for preparing a fast disintegrating thin oral film containing Valsartan. In an embodiment, the present invention provides a method for preparing a fast disintegrating thin oral film containing Valsartan, comprising: a) dissolving HPMC E5 in alcoholic solution in 100 ml beaker; b) dissolving and mixing Valsartan, Crospovidone, Dimethyl sulfoxide, and PEG 400 in the alcoholic solution of step a) to obtain a homogenous solution; c) casting the solution of step b) on a non-adhesive base plate and curing for 24 hours under an infrared lamp to obtain thin films; d) trimming the thin films of step c) into desired sizes once films are dried completely. In an embodiment, the present invention provides a fast disintegrating thin oral film containing Valsartan, wherein the HPMC E5 works as film forming agent, Polyethylene glycol 400 as plasticizer, Dimethyl Sulfoxide (DMSO) and Crospovidone used as penetration enhancer and super-disintegrant and films are prepared by solvent casting method. In an embodiment, the present invention provides a fast disintegrating thin oral film containing Valsartan, wherein the fast disintegrating film prepared by using HPMC E5 at 1:3 ratio shows better drug release up to 98.11% within 5 mins. In an embodiment, the present invention provides a fast disintegrating thin oral film containing Valsartan, wherein the SEM analysis of thin oral film indicating that the formulation shows surface texture smooth and uniform without any cracks on its surface. In an embodiment, the present invention provides a fast disintegrating thin oral film containing Valsartan, wherein the fast dissolving thin oral film comprising Valsartan useful as a potential medication agent for the treatment of hypertension and heart insufficiency. In an embodiment, the present invention provides a fast disintegrating thin oral film containing Valsartan, wherein the oral film formulation of the present invention can achieve rapid dissolution and rapid drug efficacy in the oral cavity. In an embodiment, the present invention provides a fast disintegrating thin oral film containing Valsartan, wherein the oral film formulation provides an enhanced bioavailability and a quick dissolving novel oral film drug delivery system.
Brief Description of drawings
In the drawings accompanying the specification, Figure 1 shows Drug release profiles for valsartan fast disintegrating films.
In the drawings accompanying the specification, Figure 2 shows FTIR Spectrum of optimized formulation (V9).
In the drawings accompanying the specification, Figure 3 shows SEM Photograph of optimized formulation (V9).
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides a fast disintegrating thin oral film containing Valsartan, comprising: Valsartan and pharmaceutically acceptable excipients; wherein the pharmaceutically acceptable excipients are Hydroxypropyl Methylcellulose E5, Polyethylene Glycol 400, Dimethyl sulfoxide, Crospovidone and Ethanol; wherein the weight of Valsartan 40w/w, Hydroxypropyl Methylcellulose E5 ranges from 40w/w to 160w/w, Polyethylene Glycol 400 ranges from 50w/w to 100w/w, Dimethyl sulfoxide 5w/w, Crospovidone 20w/w and Ethanol quantity sufficient; wherein the fast disintegrating thin oral film contains physical appearance as smooth, weight 275mg, drug content 40.11mg/film, Thickness 0.034mm, Folding endurance 101, dispersion test passed. The present invention provides a method for preparing a fast disintegrating thin oral film containing Valsartan, comprising: a) dissolving HPMC E5 in alcoholic solution in 100 ml beaker; b) dissolving and mixing Valsartan, Crospovidone, Dimethyl sulfoxide, and PEG 400 in the alcoholic solution of step a) to obtain a homogenous solution; c) casting the solution of step b) on a non-adhesive base plate and curing for 24 hours under an infrared lamp to obtain thin films; d) trimming the thin films of step c) into desired sizes once films are dried completely. The fast disintegrating thin oral film containing Valsartan, wherein the HPMC E5 works as film forming agent, Polyethylene glycol 400 as plasticizer, Dimethyl Sulfoxide (DMSO) and Crospovidone used as penetration enhancer and super-disintegrant and films are prepared by solvent casting method. The fast disintegrating thin oral film containing Valsartan, wherein the fast disintegrating film prepared by using HPMC E5 at 1:3 ratio shows better drug release up to 98.11% within 5 mins. The fast disintegrating thin oral film containing Valsartan, wherein the SEM analysis of thin oral film indicating that the formulation shows surface texture smooth and uniform without any cracks on its surface. The fast disintegrating thin oral film containing Valsartan, wherein the fast dissolving thin oral film comprising Valsartan useful as a potential medication agent for the treatment of hypertension and heart insufficiency. The fast disintegrating thin oral film containing Valsartan, wherein the oral film formulation of the present invention can achieve rapid dissolution and rapid drug efficacy in the oral cavity. The fast disintegrating thin oral film containing Valsartan, wherein the oral film formulation provides an enhanced bioavailability and a quick dissolving novel oral film drug delivery system.
MATERIALS AND METHODS
Valsartan a gift sample from M/S Aurobindo Pharma Ltd, Hyderabad. HPC, HPMC E5 and Polyvinyl alcohol is obtained from Mylan Pharma limited Hyderabad. PEG 400 and dimethyl sulfoxide are obtained from SD Fine Chem., Ltd., and Mumbai.
Preparation of Valsartan fast disintegrating films
Solvent casting method is used to make valsartan fast dissolving oral thin films. To obtain transparent solutions, film forming polymers such as HPC polyvinyl alcohol (PVA) and HPMC E5 are dissolved in alcoholic solutions individually in 100 ml beakers. Specified amounts of valsartan, crospovidone, dimethyl sulfoxide, and PEG 400 are weighed and dissolved in the alcoholic solution, then well mixed to obtain a homogenous solution. The resulting solution is cast on a non-adhesive base plate and cured for 24 hours under an infrared lamp. The films are trimmed into desired sizes once they had dried completely. Several attempts are conducted to improve the formula for making Valsartan fast dissolving oral thin films. The composition of Valsartan fast dissolving oral thin films as given as follows. The compositions of prepared films are given in Table 1. Based on the physiochemical and biopharmaceutical properties the aim of the present study is prepare fast disintegrating films of valsartan using solvent casting method, which should possessed a suitable approach in enhancing the disintegration and dissolution characteristics in more faster with increased bioavailability of poorly soluble valsartan drug. Hydroxyl propyl cellulose, polyvinyl alcohol and HPMC E5 are choosen as the film forming agents, Poly ethylene glycol 400 as plasticizer, Crospovidone and dimethyl sulfoxide as superdisintegrant and penetration enhancer. The valsartan fast disintegrating film formulations are prepared by 1:1,1:2 and 1:3 ratios of drug and film forming agents by solvent casting method. The composition of valsartan fast disintegrating film formulations are showed in table 1.
Table1: Composition of valsartan fast disintegrating films
Ingredients (w/w) V1 V2 V3 V4 V5 V6 V7 V8 V9
Valsartan 40 40 40 40 40 40 40 40 40
HPC 40 80 160 - - - - - -
Polyvinyl alcohol - - - 40 80 160 - - -
HPMC E5 - - - - - - 40 80 160
PEG 400 50 75 100 50 75 100 50 75 100
Dimethyl sulfoxide 5 5 5 5 5 5 5 5 5
Crospovidone 20 20 20 20 20 20 20 20 20
Ethanol QS QS QS QS QS QS QS QS QS

Evaluation of physical parameters for valsartan fast disintegrating films
The valsartan oral thin films are evaluated for physical parameters such as weight uniformity, drug content, film thickness and folding endurance. The results are given in Table 2.
Weight uniformity
The weight uniformity of the films can be done manually by using digital electronic balance.
Uniformity of drug content
An UVvisible spectrophotometric method is used to assess the drug content uniformity of the films, measuring their absorbance at a wavelength of 250 nm. The percentage drug content of various films is determined and is given in Table 2.
Film thickness
At various locations on the film, the thickness of the film is measured using a screw gauge with a least count of 0.01 mm. The average weight is calculated after measuring the film thickness at three separate locations. The obtained results are given in Table 3.
Folding endurance
Folding endurance is determined by repeatedly folding a tiny strip of film in the same spot until the film cracked, at which point the number of times the film could be folded in the same area is recorded as folding endurance. The film is folded at an angle of 1800 degrees in the same location until it broke, or it is folded 100 times without breaking. The experiments are completed in a timely manner, and the average mean is computed.
Dispersion test
Strips of film equivalent to 10mg of Drug is placed in 200 ml of pH6.8 phosphate buffer and stir with glass rod for 3 minutes and pass through 22 meshes the film is passed dispersion test only when no residue left on the mesh.
In vitro diffusion studies
Invitro diffusion studies are conducted on all the valsartan fast disintegrating films by using Franz diffusion cell apparatus containing pH 6.8 phosphate buffer as dissolution medium. The dissolution studies are carried over a period of 15 min for all the formulations. Dissolution studies are carried out in triplicate, maintaining the sink conditions for all the formulations. A 5 ml aliquot of samples is withdrawn at regular time intervals, filtered and assayed spectrophotometrically at 250 nm. The drug release profiles for all the film
formulations are shown in Figures 1.
Table 2: Evaluation of physical parameters for Valsartan fast disintegrating films
Formulation Weight uniformity
(mg) Drug content (mg/film) Film thickness (mm) Folding endurance (no) Dispersion test
V1 149 37.21 0.030 97 Passed
V2 188 38.64 0.032 98 Passed
V3 269 39.51 0.033 99 Passed
V4 148 37.11 0.031 90 Passed
V5 190 38.23 0.032 89 Passed
V6 271 39.09 0.033 92 Passed
V7 153 38.89 0.032 97 Passed
V8 192 38.90 0.033 98 Passed
V9 275 40.11 0.034 101 Passed


Evaluation of physical parameters for valsartan fast disintegrating films
The physical parameters like weight uniformity, drug content, film thickness and folding endurance are performed for all the valsartan fast disintegrating films. The weight uniformity of all valsartan fast disintegrating films prepared with hydroxyl propyl cellulose, polyvinyl alcohol and HPMC E5 are maintained in the range of 149 to 275 mg. The drug content of all valsartan fast disintegrating films is maintained in the range of 37.21 to 40.11 mg. which indicates that the drug is evenly dispersed in all the fast disintegrating film formulations. The film thickness of all fast disintegrating film formulations is maintained at the range of 0.030 ± 0.034 mm. The folding endurance values for all the fast disintegrating film formulations are maintained in the range of 89-101 foldings, which indicates that the fast disintegrating film formulations are found to be stable and should good tensile strength. The dispersion test for all the prepared films are passed. The results of evaluated parameters such as weight uniformity, drug content, film thickness and folding endurance are showed in table 2.
Invitro diffusion studies of valsartan fast disintegrating film formulations
Diffusion studies are conducted on all the valsartan fast disintegrating film formulations using Franz diffusion cell apparatus containing pH 6.8 phosphate buffer as dissolution medium. The fast disintegrating film formulations V1-V3 which are prepared by using hydroxy propyl cellulose (HPC) showed an average drug release of 91.88 to 97.67 % within 15 min. The fast disintegrating film formulations V4-V6, which are prepared by using polyvinyl alcohol (PVA), showed an average drug release of 90.81-96.23 % within 15 min. The fast disintegrating film formulations V7-V8 which are prepared by using HPMC E5 showed an average drug release of 95.11-96.23% within 15 min. when compared to the entire fast disintegrating film formulations, the fast disintegrating film formulations that are prepared by using HPMC E5 at 1:3 ratio showed better drug release up to 98.11% within 5 mins. The drug release profiles are showed in the figures 1.
Figure 1 shows Drug release profiles for valsartan fast disintegrating films
Evaluation of various invitro dissolution parameters
Dissolution parameters such as T50, T90, DE5% and first order rate constant are calculated from the dissolution data obtained, and the results are given in Table 3. All the film formulations are found to be linear with first order release rate with R2 values in the range of 0.911-0.994. Thus, the rates of drug release from all the film formulations are concentration dependent and is linear with first order release rate constant (K1). The results of the evaluation of physical parameters for valsartan oral thin films are given in the table 3.
 
Table 3: Evaluation of Invitro Dissolution Parameters for valsartan fast disintegrating films
S.No Formulation T50 (min) T 90 (min) DE 5% First order
K
(min-1) R2
3. V1 4.2 14.1 21.8 0.232 0.911
4. V2 2.1 13.5 23.7 0.211 0.933
5. V3 2.3 9.5 25.6 0.267 0.929
9. V4 4.8 14.0 22.7 0.289 0.956
10. V5 4.0 13.1 24.8 0.233 0.965
11. V6 2.2 8.6 27.9 0.255 0.956
15. V7 2.0 13.8 18.9 0.222 0.978
16. V8 1.7 12.5 26.9 0.311 0.988
17. V9 1.1 4.8 33.89 0.354 0.994
Characterization of valsartan fast disintegrating films
Based on the diffusion studies performed on all the formulations, the optimized formulations are selected and following characterization studies are done on pure drug, polymers and optimized formulation.
Fourier-Transform Infra Red (FT-IR) Spectroscopic Analysis:
To investigate the interaction between drug and carrier in films, the FTIR spectra of valsartan, HPC, PVA, and HPMC are acquired using a Brucker FTIR spectrophotometer. The samples are produced on KBr discs (two milligrammes of sample in 200 milligrammes of KBr), with a sampling range of 400-4000/cm and a resolution of 4/cm. The FTIR spectra are shown in Figures 3-6.
The FTIR spectra of valsartan exhibited principle peaks at wave numbers of 2613 cm-1 (O-H), 2963 cm-1 (C-H), 1204 cm-1(C≡N Vibrations), 1732 cm-1 (C=O Stretching), 1602 cm-1 (N-H Bending) and Aliphatic 3⁰ amine 1105 cm-1. For Hydroxy propyl cellulose the peaks are observed at 2595 cm-1 (O-H), 2927 cm-1 (C-H), 1198 cm-1(C≡N Vibrations), 1729 cm-1 (C=O Stretching), 1603 cm-1 (N-H Bending) and Aliphatic 3⁰ amine 1068 cm-1. For polyvinyl alcohol, the peaks are observed at 2581cm-1 (O-H), 2926 cm-1 (C-H), 1196 cm-1(C≡N Vibrations), 1728 cm-1 (C=O Stretching), 1602 cm-1 (N-H Bending) and Aliphatic 3⁰ amine 1068 cm-1. For HPMC E5, the peaks are observed at 2422 cm-1 (O-H), 2728 cm-1 (C-H), 1218 cm-1(C≡N Vibrations), 1559 cm-1 (C=O Stretching), 1490 cm-1 (N-H Bending) and Aliphatic 3⁰ amine 1447 cm-1. For Optimized formulation (V9), the peaks are observed at 2522 cm-1 (O-H), 2877 cm-1 (C-H), 1144 cm-1(C≡N Vibrations), 1768 cm-1 (C=O Stretching), 1640 cm-1 (N-H Bending) and Aliphatic 3⁰ amine 1218 cm-1. The spectra of optimized formulation V9 exhibited all the principle peaks present in the valsartan pure drug. Thus there is no appearance or disappearance of any characteristics peak which shows that there is no chemical interaction between the drug and the polymer used. The FTIR spectra of drug, polymers and optimized formulation V9 are shown in figure 2 and the interpretation are shown in table 4.
Figure 2 shows FTIR Spectrum of optimized formulation (V9).
Table 4: Interpretation of FTIR Spectrum
GROUP Valsartan HPC Poly vinyl alcohol HPMC E5 Optimized Formulation
(V9)
O-H Stretching 2613.05 cm-1 2595.55cm-1 2581.72cm-1 2422.89 cm-1 2522.45 cm-1
C-H Stretching 2963.20 cm-1 2927.53 cm-1 2926.22cm-1 2728.77 cm-1 2877.44 cm-1
C≡N Vibration 1204.62 cm-1 1198.42cm-1 1196.51cm-1 1218.12cm-1 1144.90 cm-1
C=O Stretching 1732.41 cm-1 1729.56cm-1 1728.85cm-1 1559.76cm-1 1768.32cm-1
N-H Bending 1602.40 cm-1 1603.78cm-1 1602.52cm-1 1490.22cm-1 1640.11cm-1
Aliphatic 3⁰ amine 1105.70 cm-1 1068.98cm-1 1068.81cm-1 1447.18cm-1 1218.65cm-1
Scanning electron microscopy analysis
The SEM photographs are taken for the optimized film formulation V9 and Valsartan pure drug. The SEM photographs are shown in figures. The SEM analysis are performed for valsartan pure drug and optimized formulation V9, The results indicated that the optimized formulation V9 showed surface texture is smooth and uniform without any cracks on its surface.
Figure 3 shows SEM Photograph of optimized formulation (V9).
CONCLUSION
Valsartan oral thin films prepared by solvent casting method showed good flexibility and film characteristic properties. The optimized formulation V9 containing HPMC E5 at 1:3 ratio released the drug 98.11% within 5 mins, which is desirable for faster dissolution and absorption. Valsartan oral thin films prepared by solvent casting technique are found to be suitable for the prevention and treatment of hypertension.
REFERENCES
1. Bajaj H, Bisht S, Yadav M, Singh V. Bioavailability enhancement: A review. Int J pharma. Bio. Sci. 2011; 2: 202-15.
2. Dixit RP, Puthli SP. Oral strip technology: Overview and future potential. Journal of Controlled Release 2009; 139: 94-07.
3. Vollmer U, Galfetti P. Rapid Film: Oral Thin Films as an Innovative drug delivery system and dosage form. Drug Development Report 2006; 2: 1-5.
4. Mahajan A, Chhabra N, Agarwal G. Formulation and Characterization of fast dissolving buccal film: A Review. Der Pharmacia Sinica 2011; 3: 152-65.
5. Suresh B, Halloran D James L. Quick Dissolving Films: A Novel approach to drug delivery. drug development technology 2006; 3: 1-7.
6. Gavaskar B, Kumar SV, Sharan G, Madhusudan Y. Overview on Fast dissolving films. Int. J. Pharm. Pharm. Sci. 2010; 3: 29-33.
7. Prabhu P, Malli R, Koland M, Vijaynarayana K, Souza U, Harish N. Formulation and evaluation of fast dissolving films of levocitirizine dihydrochloride. Int J Pharm Investig 2011; 1: 99-04.
8. Tora GJ, Gorahowski SR. Principles of Anatomy and Physiology. Wiley & Sons, Incorporated, John: Harpet Tora Tora Gorahowski 1992; 7: 770-74.
9. Beg S, Swain S, Singh HP, Patra CN, Rao MB. Development, optimization and characterization of solid self-nanoemulsifying drug delivery systems of valsartan using porous carriers. Pharm Sci Tech 2012; 2: 112-14.
10. Markham A, Goa KL. Valsartan: a review of its pharmacology and therapeutic use in essential hypertension. Drugs 1997; 54: 299-11.
11. Flesch G, Lloyd P, Muller PH. Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man. Eur J Clin Pharmacol 1997; 52: 115-20.
12. Rajesh K, Prasanna Raju Y, Nagaraju R, Dissolution enhancement of valsartan using natural polymers by solid dispersion technique. Der Pharmacia Lettre 2013; 5: 126-34.
13. Vidyadhara S, Sasidhar RLC, Balakrishna T, Santhavardhan M. Formulation of rizatriptan benzoate fast dissolving buccal films by emulsion evaporation technique. Int. J. Pharm.Investing. 2015: 5: 101-06.
14. Balakrishna T, Vidyadhara S, Murthy TEGK, Sasidhar RLC. Formulation and evaluation of lansoprazole fast dissolving buccal films. Asian J. Pharm. 2018: 12: 101-35.
15. Balakrishna T, Vidyadhara S, Murthy TEGK, Ramu A, Sasidhar RLC. Formulation and evaluation of esomeprazole fast dissolving buccal films. Asian J Pharm Clin Res. 2018: 11: 193-99.
16. Balakrishna T, Vidyadhara S, Murthy TEGK, Sasidhar RLC, Venkateswarao J. Formulation and evaluation of lansoprazole fast dissolving buccal films. Asian J. Pharm. 2016: 10: 313-19.
17. Balakrishna, T., 2022. Development and Evaluation of Valsartan Fast Disintegrating Films. Asian Journal of Pharmaceutics (AJP), 16(1).
, Claims:1. A fast disintegrating thin oral film containing Valsartan, comprising:
Valsartan and pharmaceutically acceptable excipients;
Wherein the pharmaceutically acceptable excipients are Hydroxypropyl Methylcellulose E5, Polyethylene Glycol 400, Dimethyl sulfoxide, Crospovidone and Ethanol;
Wherein the weight of Valsartan 40w/w, Hydroxypropyl Methylcellulose E5 ranges from 40w/w to 160w/w, Polyethylene Glycol 400 ranges from 50w/w to 100w/w, Dimethyl sulfoxide 5w/w, Crospovidone 20w/w and Ethanol quantity sufficient;
wherein the fast disintegrating thin oral film contains physical appearance as smooth, weight 275mg, drug content 40.11mg/film, Thickness 0.034mm, Folding endurance 101, dispersion test passed.
2. A method for preparing a fast disintegrating thin oral film containing Valsartan, comprising:
a) dissolving HPMC E5 in alcoholic solution in 100 ml beaker;
b) dissolving and mixing Valsartan, Crospovidone, Dimethyl sulfoxide, and PEG 400 in the alcoholic solution of step a) to obtain a homogenous solution;
c) casting the solution of step b) on a non-adhesive base plate and curing for 24 hours under an infrared lamp to obtain thin films;
d) trimming the thin films of step c) into desired sizes once films are dried completely.
3. The fast disintegrating thin oral film containing Valsartan, as claimed in claim 1-2, wherein the HPMC E5 works as film forming agent, Polyethylene glycol 400 as plasticizer, Dimethyl Sulfoxide (DMSO) and Crospovidone used as penetration enhancer and super-disintegrant and films are prepared by solvent casting method.
4. The fast disintegrating thin oral film containing Valsartan, as claimed in claim 1-2, wherein the fast disintegrating film prepared by using HPMC E5 at 1:3 ratio shows better drug release up to 98.11% within 5 mins.
5. The fast disintegrating thin oral film containing Valsartan, as claimed in claim 1-2, wherein the SEM analysis of thin oral film indicating that the formulation shows surface texture smooth and uniform without any cracks on its surface.
6. The fast disintegrating thin oral film containing Valsartan, as claimed in claim 1-2, wherein the fast dissolving thin oral film comprising Valsartan useful as a potential medication agent for the treatment of hypertension and heart insufficiency.
7. The fast disintegrating thin oral film containing Valsartan, as claimed in claim 1-2, wherein the oral film formulation of the present invention can achieve rapid dissolution and rapid drug efficacy in the oral cavity.
8. The fast disintegrating thin oral film containing Valsartan, as claimed in claim 1-2, wherein the oral film formulation provides an enhanced bioavailability and a quick dissolving novel oral film drug delivery system.

Documents