Preparation and Evaluation of Fast Dissolving Oral Film of Losartan Potassium

 

Sara Sadique¹*, Ramya Sri S.²

¹Department of Pharmaceutics, Global College of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad, Telangana, India.

²Department of Pharmacy, University College of Technology, Osmania University, Hyderabad, Telangana, India.

 

ABSTRACT:

The fast dissolving oral film of losartan potassium were prepared using different polymers like PVP, HPMC and Pectin by solvent casting method. The fast dissolving oral film evaluated for folding endurance, swelling index, surface pH, in vitro disintegration time, drug content, drug polymer compatibility (IR Study), and in vitro drug release. The physical appearance and folding endurance properties were found to be good. The average folding endurance time within the range of 112 to 208. The drug content showed uniform mixing of drug in all prepared fast dissolving films. The in vitro drug release showed 78 to 96 % drug release within 5 minutes. Drug release obeys the first order kinetics. Hence it can be inferred that the fast dissolving oral film of losartan potassium may produce the rapid action thereby improving bioavilability and enhance the absorption by avoiding the first pass effect.

 

 

 

INTRODUCTION:

Recent developments in technology have presented viable dosage alternatives for patients who may have difficulty in swallowing of tablets or liquids. Conventionally oral solid dosage form are administered with a glass of water may be inconvenient or impractical for some patients¹. The oral cavity has been investigated as a site for drug delivery from a long period of time. about 60% of the total dosage form are administered by oral route². Among the different routes of administration, the oral route of administration continues to be most preferred route due to various advantages including ease of administration, avoidance of pain, versatility and most importantly patient compliance.

 

One such relatively new dosage form is the oral strip, a thin film that is prepared using hydrophilic polymers that rapidly dissolves on the tongue or buccal cavity. Recently, fast dissolving drug delivery system have started gaining popularity and acceptance as new drug delivery systems, because they are easy to administer and lead to better compliance. These delivery systems either dissolve or disintegrate in mouth rapidly, without requiring any water to aid in swallowing³. They also impart unique product differentiation, thus enabling use as line extensions for existing commercial products. This novel drug delivery system can also be beneficial for meeting the current needs of the industry for improved solubility/stability, biological half life and bioavailability enhancement of drugs⁴.

 

Many pharmaceutical dosage forms are administered in the form of pills, granules, powders and liquids. Generally, a pill is designed for swallowing intact or chewing to deliver a precise dosage of medication to patients. The pills, which include tablet and capsules, are able to retain their shapes under moderate pressure. However, some patient, particularly pediatric and geriatric patients, have difficulty in swallowing or chewing solid dosage forms^5,6.

 

MATERIALS AND METHOD:

Materials:

Losartan potassium was Provided by Sura Labs, Dilsukhnagar, Hyderabad. Poly vinyl pyrrolidone k-30, HPMC E-15, Pectin, Aspartame, Propylene glycol, Sodium starch glycolate gifted from SD Fine Chem. Ltd. Mumbai.

 

METHODOLOGY:

Preparation of fast dissolving oral film of losartan potassium:

Oral fast dissolving film was prepared by solvent casting method. Aqueous solution I was prepared by dissolving film forming polymer, in specific proportion in distilled water and allowed to stirred for 3 hours and kept for 1 hour to remove all the air bubble entrapped or remove bubbles. Aqueous solution II was prepared by dissolving the pure drug, sweetner, and plasticizer in specific proportion in distilled water. The aqueous solution I and II were mixed and stirred for 1 hour. The solution _{were cast on to 9cm diameter petri dish and were dried in the oven at 450C for 12} hours. The film was carefully removed from surface of petridish and cut according to size required for testing (square film 1.5cm length, 1.5cm width). The samples were stored in glass container maintained at a temperature 30⁰C and relative humidity 60% ± 5% until further analysis.

 

Formulation of fast dissolving film of losartan potassium:

Calculation of dose for losartan potassium:

The dose of losartan potassium is 25mg. Therefore amount of losartan potassium required in 3cm (1.5x1.5) is 25mg.

i)      Area of film of 1.5X1.5sq.cm is 2.25sq.cm.

ii)  Area of petridish of 6cm diameter is 28.26sq.cm.

iii)           Amount of drug present in 2.25sq.cm of film is 25 mg.

iv) Amount of drug present in 28.26sq.cm of petridish is 314mg.

 

Therefore, 2.25sq.cm of film should contain 25mg of drug. It is fixed for all formulation.

 

_{Formulation details of fast dissolving oral film of losartan potassium.}

INGRIDIENTS	F1	F2	F3	F4	F5	F6	F7	F8	F9
Drug (m.g)	300	300	300	300	300	300	300	300	300
HPMC (mg)	0.5	1.0	1.5	_	_	_	_	_	_
PVP (mg)	_	_	_	0.5	1.0	1.5	_	_	_
Pectin (mg)	_	_	_	_	_	_	0.5	1.0	1.5
Glycerine (ml)	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5	0.5
Propylene Glycol (ml)	0.25	0.25	0.25	0.25	0.25	0.25	0.25	0.25	0.25
Aspartame (mg)	0.6	0.6	0.6	0.6	0.6	0.6	0.6	0.6	0.6
Lactose (mg)	100	100	100	100	100	100	100	100	100
Sodium Citrate (mg)	0.01	0.01	0.01	0.01	0.01	0.01	0.01	0.01	0.01
Preservative (mg)	0.05	0.05	0.05	0.05	0.05	0.05	0.05	0.05	0.05
S.S.G (%)	--	--	1	--	--	1	--	--	1
Water (make upto. ml)	10	10	10	10	10	10	10	10	10

 

Evaluation Parameters:

Physical appearance and surface texture of the film:

This parameter was checked by doing visual inspection of films and texture of films is evaluated.

 

Thickness of film:

Thickness of the film was measured using screw guage with a least count of 0.01mm at different spots of the film. The thickness was measured at three different spots of the film and average was taken.

 

_{Folding endurance:}

Folding endurance is determined by repeated folding of the whole film at the same place till the film breaks. The number of times the film is folded without breaking is computed as the folding endurance value.

 

Moisture uptake:

The moisture uptake of the films are determined by exposing them to an environment of 40⁰C with 75% relative humidity for 1 week. The uptake of moisture by the films was calculated with percent increase in weight.

 

Uniformity of drug content:

This parameter was determine by dissolving one film of dimension 1.5X1.5cm containing 25mg of losartan potassium by homogenization in 100ml of PH 6.8 phosphate buffer for 30 minutes with continues shaking. From this, 10ml was diluted to 50ml using PH 6.8 buffer solution. The absorbance was measured at 203nm.

_{In-vitro disintegration study:}

The in-vitro disintegration of the fast dissolving oral film were determined using disintegration test apparatus. Place one piece of film in each of the six tubes of the basket. Add the disc to each tube and run the apparatus using 900ml of pH 6.8 phosphate buffer solution as the immersion liquid. The assembly should be raised and lowered between 30 cycles per _{minute in distilled water maintained at 37º±0.50C. The time in seconds for complete} disintegration of the oral film with no palable mass remaining in the apparatus was measured and recorded.

 

_{In-vitro dissolution study:}

The in-vitro release of fast dissolving oral film of losartan potassium was carried out using basket type electrolab tablet dissolution tester USPXXIII. Drug load film equivalent to 25mg of drug was introduced in to the 900ml of the dissolution medium pH 6.8 phosphate buffer maintained at 37±0.5⁰C with basket rotating at 50 rpm. Aliquates are withdrawn at regular intervals and analyzed spectrophotometrically. The dissolution studies were carried out in triplicate in pH 6.8 phosphate buffer for 5 minutes. The volume of dissolution medium was adjusted to 900ml at every sampling time by replacing 5ml with same dissolution medium. And then it was analysed by using spectrophotometer at 203nm.

 

RESULTS AND DISCUSSION:

Table: Standard calibration curve of losartan potassium in 6.8 Ph phosphate buffer solution at λ_max 203nm

Sl. No	Concentration (mcg/ml)	Absorbance
1	0.00	0.00
2	01	0.182
3	03	0.300
4	05	0.493
5	07	0.695
6	09	0.903

 

 

Fig: standard calibration curve of losartan potassium

 

 

Table: Evaluation of fast dissolving oral film of losartan potassium

 

Table: Evaluation of fast dissolving oral film of losartan potassium

Formulation Code	Weight (mg)	Moistureuptake	Thickness (mm)	Floding Endurance
F1	48.00 ± 1.00	Nil	0.7±0.115	112±2.517
F2	47.66±1.528	Nil	0.8±0.057	123±3.215
F3	47.21±1.00	Nil	0.7±0.057	123±4.726
F4	50.32±1.432	Nil	1.1±0.010	144±3.215
F5	43.10±0.522	Nil	0.9±0.152	133±4509
F6	47.10±0.574	Nil	0.9±0.200	149±2.082
F7	56.25±0.362	Nil	1.1±0.173	171±3.606
F8	57.45±0.220	Nil	1.1±0.100	184±4.041
F9	60.29±1.210	Nil	1.1±0.100	197±2.517

 

Table: In vitro drug release profile of Losartan potassium from F1 to F9

TIME (SEC)	F1	F2	F3	F4	F5	F6	F7	F8	F9
0	0	0	0	0	0	0	0	0	0
30	26.95	20.49	19.12	2.27	10.69	8.15	4.62	1.06	5.80
60	37.87	34.31	30.39	12.27	27.09	26.02	20.51	12.65	18.56
90	59.24	57.03	51.32	39.18	45.38	42.22	38.74	37.79	39.82
120	72.10	73.60	70.01	61.92	66.00	59.10	60.63	59.15	66.68
150	88.56	85.17	86.07	83.80	82.43	79.60	78.40	75.54	78.99

 

 

 

Fig: In vitro drug release profile of fast dissolving oral film of losartan potassium

 

CONCLUSION:

In the present work, the fast dissolving film of losartan potassium were prepared by solvent casting method, by using the different concentration of the polymers and super disintegrants like sodium starch glycolate and crosormollose sodium. Losartan potassium is soluble in water but its bioavailablity is limited. Hencethis fast dissolving film is useful for the improving of the bioavailability of the drug. All the fast dissolving film of losartan potassium were subjected to physical appearance, moisture uptake, average weight uniformity, surface PH, folding endurance, swelling index, drug content uniformity, in vitro disintegration time and in vitro drug release study. Based on the above evaluation following conclusion can be drawn.

 

The FTIR study confirmed that the polymer were found to be compatible with losartan potassium. The results shows that no chemical interaction taken place during formulation of the films were reversible and not irreversible.

·       The films prepared checked visually for its appearance and texture. All the films are smooth surface and good appearance.

·       All the prepared films (F1-F9) were checked for thickness by using screw guage micrometer, all the films were found to be within the range of 0.7mm ± 0.115 to 1.1mm ± 0.010, with the minimum standard values indicates that all the films are uniform in thickness.

·       All the prepared films (F1-F9) evaluated for folding endurance, the values found to be in the range of 112 ± 2.517 to 208 ± 2.887. Formulation F1 and F11 shows with the range of 112 ± 2.517 and 128 ± 3.055 indicates the excellent flexibility among other formulations.

·       The all prepared films were subjected to swelling index, F1, F4, F11, F14, and F15 shows the maximum swelling index i.e 64.65 ± 2.263 to 71.16 ± 3.608 as compared to the other formulations, indicates the better swelling ability between the water and polymers.

·       The prepared fast dissolving films are evaluated for drug content uniformity, all the formulations are within the range of 88.33 ± 0.027 to 98.68 ± 0.034. Formulation F3, F5, F11, F14, and F15 shows the better and uniform drug content in the films.

·       The fast dissolving films were subjected to average in vitro disintegration time, and all the formulation within the range of 19 ± 3.606 to 49 ± 2.887. Formulation F1, F2, F3, F11, F12, F14 and F15 shows the good disintegration time.

·       The fast dissolving film were subjected to the in vitro drug release study for a period of 5 minutes. All the formulations, released more than 75% to 97% drug within 5 minutes.

·       It was observed that, formulation F1 which is prepared with 2% PVA, 0.5% PVP showed 88.56% drug release and formulation F2 which is prepared with 2% HPMC with 0.5% PVP showed 85.17% drug release within 2 min and 30 seconds.

 

АCKNOWLEDGEMENT:

Thе authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе nеcеssary facilitiеs for thе rеsеarch work.

 

REFERENCES:

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2.      Kulkarni AS, Deokule HA, Mane MS, Ghadge DM. Exploration of different polymers for use in the formulation of oral fast dissolving strips. journal of current pharmaceutical research 2010; 2(1): 33-35.

3.      Kumar D, Rathi L, Tipathi A, Maddheshiya YP. A review of oral mucosal drug delivery system. International journal of pharmaceutical science and research 2010; 1(5): 50-56.

4.      Slowson M, slowson, S. What do when patients cannot swallow their medications. Pharma Times.1985;51:90-96.

5.      Tora –Tora Gorahowski. Principles of Anatomy and Physiology, 7th Edition edited by Gerad j. Tora-Tora and Sandro Reynolds Gorahowski, published Harpet Collins College Publishers; 1992:770-4.

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Received on 21.01.2020         Modified on 08.02.2020

Accepted on 19.02.2020       ©A&V Publications All right reserved