Incorporation of Antihypertensive Class IV Drug in Novel Buccal Film Formulation

 

Adesh Yelave, Geeta Sameer Bhagwat, Adnan Rehmatullah Siddique

¹HK College of Pharmacy, HK Campus, Relief Road, Oshiwara,

Jogeshwari West, Pratiksha Nagar, Mumbai, Maharashtra 400102.

²DY Patil University School of Pharmacy, Nerul Sector - 7, Navi Mumbai 400706.

³HK College of Pharmacy, HK Campus, Relief Road, Oshiwara,

Jogeshwari West, Pratiksha Nagar, Mumbai, Maharashtra 400102.

 

ABSTRACT:

Chlorthalidone is a thiazide-like diuretic drug used in the treatment of hypertension. It belongs to class IV of Biopharmaceutical Classification System (BCS) and exhibits first pass metabolism leading to low bioavailability. The present work was undertaken to formulate mucoadhesive buccal film of chlorthalidone with an objective to improve bioavailability, therapeutic efficacy, and patient compliance. Film formulations were prepared by solvent casting method using a combination of different grades of hydrophilic polymer, Hydroxypropyl methylcellulose with suitable plasticizer. Other important excipients used were solubilizing agents to increase solubility and permeation enhancers to increase the permeability of the drug. The developed films were evaluated for physicochemical characteristics such as thickness, content uniformity, surface pH, and in vitro drug release etc. The optimized formulation containing a combination of hydrophilic and hydrophobic polymers showed good tensile strength, mucoadhesive strength and optimum in vitro diffusion results. The Ex vivo Drug permeation through porcine oral mucosa at the end of 8 hours was found to be 87.2±0.93%.

 

 

 

1.    INTRODUCTION:

Oral route is considered as most preferred and convenient amongst all routes of administration. Drugs administered through oral route are either susceptible to hepatic first pass metabolism or gastrointestinal degradation or both¹. The transmucosal drug delivery system includes ocular, oral mucosa, nasal, rectal and vaginal can offer the potential alternative solution for delivery of drugs. The mucoadhesive polymers used in the formulations have high molecular weight and or high viscosity². Buccal mucosa is preferred as an ideal site amongst mucoadhesive transmucosal drug delivery, because it contains smooth muscles with high vascularization of blood vessels and avoids hepatic first pass metabolism¹ Mucoadhesive buccal films are more prominent and convenient for dosage form amongst other approaches such as buccal spray, gels, tablets, wafers, microparticles owing to its longer contact time³.

 

Chlorthalidone is a thiazide diuretic, used mainly in the treatment of hypertension. Chlorthalidone exist in four different polymorphic forms i.e Form I, Form II, Form III, and Form IV. Among all the four forms Form 1 is the most stable polymorph. However the most stable polymorph of chlorthalidone has low bioavailability up to 65% because gastrointestinal degradation and hepatic first pass metabolism. To improve its bioavailability, drug can be administered through buccal mucosa through buccal films^1,2. Buccal delivery of chlorthalidone may surpass GI degradation and first pass metabolism and may contribute to improve its bioavailability. In present study, attempt was made to formulate mucoadhesive buccal film of chlorthalidone using combination of Cellulose polymers as mucoadhesive polymer along with suitable plasticizer. The efficacy of developed films was confirmed by their in-vitro drug release profile and ex-vivo permeation evaluation.

 

2.    MATERIALS AND METHOD:

2.1.    Materials used:

Chlorthalidone was obtained as gift sample from CTX life sciences, Surat, Gujrat. HPMC K4M, HPMC E5 and ethyl cellulose (5 cps, 20 cps, and 40 cps) were obtained as gift sample from Colorcon Pvt Ltd, Goa. Sodium deoxytaurocholate (SDC) and sodium saccharin were procured from vishal chemicals. All the solvents and reagents used were of analytical grade.

2.2.    PREFORMULATION STUDIES:

A.   Identification tests:

1.     Determination of melting point of chlorthalidone:

Melting point of chlorthalidone was measured by an open capillary method using melting point apparatus.

2.     FTIR spectroscopy:⁴

FTIR spectrum of drug sample was determined using an IR spectrometer (IR Affinity S1, Shimadzu). The determined FTIR spectrum of drug sample was compared with standard FTIR of pure drug to find any significant changes in drug sample.

3.     XRD studies:⁵

XRD studies of Procured drug was done using X-ray diffractometer to identify that which polymorphic form of drug was obtained

4.     Solubility analysis:⁶

10mg of drug was dissolved in 10ml of selected solvents like distilled water, ethanol, methanol, phosphate buffer pH 6.8 and phosphate buffer pH 7.4. Then, these solutions are observed visually for the presence of any undissolved drug particles.

5.     Determination of absorption maxima (λ_max) of drug:

10ppm solution of chlorthalidone was prepared using phosphate buffer pH 6.8. The solution was analyzed from 250 to 350nm to determine absorption maxima (λ_max).

B.    Compatibility study by FTIR spectroscopy:

FTIR spectrum of chlorthalidone, a physical mixture of chlorthalidone and excipients of buccal film and, a physical mixture of chlorthalidone and excipients of backing membrane was recorded by FTIR (IRAffinity S1, Shimadzu) instrument.

C.   Standard calibration curveof Chlorthalidone in phosphate buffer pH 6.8 and pH 7.4:⁷

10mg of drug was dissolved in 1ml of methanol and the volume was adjusted to 100ml of phosphate buffer pH 6.8 to get 100ppm stock solution. Further dilutions were prepared to get 4 to 36ppm solutions. Same procedure was done to prepare dilutions from 4 to 24ppm using phosphate buffer pH 7.4. The absorbances are recorded at 275nm using a UV spectrophotomer. The graph of absorbance v/s concentration (ppm) was plotted.

 

2.3.    METHOD OF PREPARATION:^8–10

A.   Buccal film:

HPMC K4M and HPMC E5 were accurately weighed and soaked in ethanol for 2 hours. Then small amount of distilled water was added and kept it on magnetic stirrer for 15 minutes at 500rpm. Plasticizer (propylene glycol) was added in it and stirred it again on magnetic stirrer for 10minutes. Sodium deoxytaurocholate (SDC) was added and stirred for 15minutes. Volume was made up with distilled water: ethanol (1:1) solution. The API, chlorthalidone was accurately weighed in such way that 4 cm² films contains 12.5mg drug and then dissolved in methanol in another beaker. The polymeric solution was added in drug solution and was mixed thoroughly with the help of magnetic stirrer for 1hour at 500rpm. For deaeration, the solution was kept on ultrasonicator until air bubbles were removed. The final solution was then poured in petriplate. Then petriplate was kept in oven for 24hours at 50°C for complete drying. After drying, the films were observed for their physical appearance. The films were cut into 2cm Χ 2cm dimension. To get an optimized buccal film different concentrations of polymer were used in each batch from F1 to F9 which is mentioned in table no 1

 

Table no. 1: Composition of mucoadhesive buccal films

 

B.    Backing membrane:

Ethyl cellulose was dissolved in mixture of Acetone: Isopropyl alcohol (1:3) and stirred using magnetic stirrer at 100rpm for 3 hours. Plasticizer was added as per formula and stirred again for 3hours at 250rpm. The polymeric solution was poured in prelubricated petriplate and inverted funnel was placed over dish to avoid sudden evaporation of solvents. Then petriplate was placed at room temperature for 12hours for drying. The dried film was removed from mould and cut into 3cmΧ3cm dimension.To get an optimized backing membrane formula varied combination of material used in varied concentrations from B0 to B9 which is mentioned in table no 2

Table no. 2: Composition of backing membrane

 

3.     CHARACTERIZATION OF CHLORTHALIDONE LOADED BUCCAL FILM:^11–13

1)    Physical appearance:

The prepared films was observed and checked for visible imperfections and surface texture by feel and touch.

2)    Weight variation:

Three films of every formulation were weighed individually using electronic weighing balance. The mean weight was recorded.

3)    Thickness of film:

Thickness of film was measured by using a micrometer screw gauge (Mitutoyo, Japan). Thickness was recorded from 5 different positions (4 corners and center) and the mean was calculated.

4)    Folding endurance:

Folding endurance of film was determined by repeatedly folding the corner of film till it brokes. The mean value was calculated.

5)    Surface pH

pH of the buccal film was measured using Surface pH meter where 1ml of distilled water was placed on surface of buccal film and kept it for 1hour and tip of electrode of pH-meter was touched to moistened surface of buccal film and allowed it to equilibrium for 1 minute, and the mean pH was recorded .

6)    Drug content uniformity:

The three films of each formulation were taken in separate 100 volumetric flasks and phosphate buffer pH 6.8 was added. It was sonicated for 24hours. From this solution, 5ml of sample was withdrawn and diluted to 100ml using phosphate buffer pH 6.8. Then it is analyzed at 275.8nm. The mean of drug content was recorded as final reading of drug content.

7)    Swelling index:

3 films of pre-determined weight (initial weight) were taken and kept in petriplate containing 5ml of phosphate buffer pH 6.8 for 6 hours at 37°C. After 6 hours, the swelled films were removed and reweighed (final weight). The swelling index was calculated using formula,

 

Swelling index = [(W₂-W₁)/W₁] × 100

Where, W₂ is weight of swollen film at 6 hours, W₁ is weight of dry film at zero time.

 

8)    Percent moisture absorption:

The three films of each formulation were taken and kept in a desiccator containing 100ml of ammonium chloride upto 96% humidity for 3 days. After 3 days, films were removed and reweighted. The percent moisture absorption was calculated using formula,

% moisture absorption = [(W₂-W₁)/W₁] × 100

Where, W₁ is initial weight of dry film and W₂ is final weight of film after 3 days

9)    Percent moisture loss:

The three films of each formulation were taken and kept in desiccator containing fused anhydrous calcium chloride for 72 hours for moisture loss. After 72 hours, films were removed and reweighed⁶. The percent moisture loss was calculated using formula,

% moisture loss = [(W₁-W₂)/W₁] × 100

Where, W₁ is initial weight of dry film and W₂ is final weight of film after 3 days

10)  Mucoadhesive strength:

The mucoadhesive strength of developed films was determined by in-house method. Two arm balances was used for determination of mucoadhesion. To left side, a solid support was glued at bottom and glass slide was tied on that side and on right side pan, weight was placed. On left side, mucoadhesive buccal film was hydrated with distilled water and pressed it to glass slide. Then glass slide was pressed to fixed solid support. On right hand side pan, weight was added gradually so that film would be detached. Mucoadhesive strength was determined by weight required to detach the film from fixed solid support

11) Tensile strength:

Tensile strength of developed films was determined by in-house method. 2 arm analytical balance was used to determine tensile strength. To left side, one end of buccal film was tied to fix solid support at bottom and one end was tied upward, and on right hand side pan, weight was placed. During the measurement, weight was added gradually to right side pan so that due to stress the film would break^11,14. The weight at which film breaks was recorded for further calculation.

 

Tensile strength= (force applied/cross sectional area of film) = [(m*g)]/[(w*t)]

Where, m is weight required breaking film; g is acceleration due to gravity; w is width of film and, t is thickness of film.

 

12) in-vitro drug release:¹⁵

Dissolution test apparatus type IVwas used to study the in-vitro drug release profile using isotonic phosphate buffer solution (PBS) pH 6.8 at 50 rpm at 37±0.5˚C for time period of 8 hrs. The film was pasted to a watch glass with cyanoacrylate adhesive and Stainless steel wire mesh was fixed securely on the watchglass so that it doesn’t touch the film yet secures the film at the bottom¹⁴. This assembly was placed at bottom of the dissolution flask as shown in fig 1. The flask was filled with 250ml phosphate buffer pH 6.8. The sample (aliquot) of 5 ml was taken out at regular intervals and replaced with fresh phosphate buffer pH 6.8. Then the aliquot was filtered and analyzed by UV Spectrophotometer at 275.8nm

 

Fig No. 1: Dissolution assembly

 

13)  In-vitro Drug release in CD14 Dissolution apparatus :¹⁶

CD-14 Dissolution test apparatus type 4 was used to study the in-vitro drug release profile of the final optimized batch using isotonic phosphate buffer solution (PBS) pH 6.8 at 50rpm at 37±0.5˚C for time period of 8 hrs. The film was fix on to a watch glass and was clipped with Stainless steel wire mesh was fixed securely on the watch glass so that it doesn’t touch the film yet secures the film at the bottom. This assembly was placed at bottom of the dissolution flask (Figure no 2). The flask was filled with 250ml phosphate buffer pH 6.8. The sample (aliquot) of 5ml was taken out at regular intervals and replaced with fresh phosphate buffer pH 6.8. Then the aliquot was filtered and analyzed by Spectrophotometer at 275.8nm

 

 

Fig no 2 Dissolution assembly for CD14 Dissolution apparatus

 

14)  In-vitro diffusion studies:¹⁷

In-vitro diffusion studies were performed using modified franz diffusion cell across dialysis membrane of molecular weight 12000-14000 Dalton and pore size 2.4 nm (HIMEDIA Pvt Ltd).

 

Preparation before studies:

The membrane was washed with running water for 3-4 hours to remove glycerols. Then membrane was treated with 0.3% solution of sodium sulfide at 80°C for 1 min to remove sulfur compounds. Afterwards it was washed with hot water (60°C) for 2 minutes, followed by acidification with 0.2% solution of sulfuric acid, then rinsed with hot water to remove the acid. The membrane was then soaked in distilled water overnight before use.

 

The receptor compartment was filled with phosphate buffer pH 6.8. The membrane was placed between donor and receptor compartment. The assembly was kept for 15 minutes to stabilize the membrane. Then 1.5 Χ 1.5 cm² of developed buccal film was placed on top of the membrane. The hydrodynamics was maintained by stirring with magnetic bead at 50±5RPM and temperature was maintained at 37±0.5˚C. The sample (1 ml) was withdrawn at regular intervals and replaced with fresh phosphate buffer. Then the aliquot was diluted and analyzed by spectrophotometer at 275.8nm¹⁸

 

15) Drug release from backing membrane:

To determine efficacy of the backing membrane, drug release study was done using USP type II apparatus using phosphate buffer pH 6.8 at 50rpm 37±0.5˚C for the same time as of buccal film. The film was pasted on watch glass and backing membrane was pasted on it using cyanoacrylate glue. The same procedure was repeated as of used for in-vitro drug release study to check the release of drug from backing membrane.

 

16)  Ex-vivo permeation studies:¹⁹

The permeation studies were carried out by modified franz diffusion cell using phosphate buffer pH 7.4 as medium. The receptor compartment was filled with phosphate buffer pH. The bovine mucosa was procured from local slaughter house. The mucosa was cleaned thoroughly and fatty latyer was removed carefully. Then mucosa was placed between donor and receptor compartment. The assembly was kept for 15 minutes to stabilize the mucosal membrane. Then 1.5 Χ 1.5 cm² of developed buccal film was placed on the membrane. The hydrodynamics was maintained by stirring with magnetic bead at 50 rpm and temperature was maintained at 37±0.5˚C. The sample (1ml) was withdrawn at regular intervals and replaced with fresh phosphate buffer. Then the aliquot was diluted and analyzed by spectrophotometer at 275.8nm ²⁰.

 

4.    RESULTS:

A.   Identification tests:

1.    Determination of melting point of drug:

The melting point of chlorthalidone was found to be 239˚C which complies with COA of drug provided by manufacturing industry. It also matches with the literature data that have been published.⁶

 

2.    FTIR spectroscopy:

The FTIR spectrum of the drug sample was found to be similar to reference standard FTIR of pure drug²¹(Fig no 3A and 3B)

 

Fig No. 3A: FTIR spectrum of Reference Standard                                Fig No. 3B : FTIR spectrum of drug sample

 

Table no 3 Different polymorphic form of Chlorthalidone

 

Fig no 4 XRD pattern of Chlorthalidone

 

Table no 4 XRD data of Chlorthalidone

 

XRD studies:

Chlorthalidone exist in 4 polymorphic forms: Form 1, Form 2, Form 3, Form 4

Based on the comparison of the XRD pattern of form 1 and form 2 obtained from literature with our drug (Figure no 4) it was found that our drug sample has a similar XRD pattern with the form 1 because most of the prominent peak of form 1 are present in our drug with good intensities. No prominent peak of form 2 was observed in our drug XRD which confirms our drug sample contains polymorphic form 1 of chlorthalidone which has low aqueous solubility.

 

 

 

3.    Solubility studies:

Chlorthalidone was found to be insoluble in distilled water, phosphate buffer pH 6.8, and phosphate buffer pH 7.4, slightly soluble in ethanol and soluble in methanol.

 

4.    Determination of absorption maxima (λ_max) of drug:

The wavelength scan 250-350 nm was performed to find the absorption maxima of chlorthalidone. Absorption maxima of chlorthalidone were found to be 275.8nm and 284.2nm (Figure no 5). UV spectrum of drug sample was similar to reference standard UV spectra of pure chlorthalidone as per I.P.

 

 

Fig No. 5: UV spectrum of chlorthalidone drug sample

 

 

Fig No. 6: FTIR spectra of chlorthalidone, a physical mixture of chlorthalidone and excipients of buccal film and, a physical mixture of chlorthalidone and excipients of backing membrane

 

B.    Compatibility studies by FTIR spectroscopy:

FTIR spectrum of chlorthalidone, a physical mixture of chlorthalidone and excipients of buccal film and, a physical mixture of chlorthalidone and excipients of backing membrane was shown in fig no. 6. It was observed that the fundamental peaks correspond to the major functional groups of chlorthalidone are observed. The peak at 3240 cm^-1 assigns to N-H stretching of amine, 1345 cm^-1 assigns sulfonamide group and, 1038 cm^-1 assigns O-H bending. All fundamental peaks of drug are shown in both physical mixtures as shown in fig 6. Thus chlorthalidone was considered as compatible with all excipients used in buccal film and backing membrane.

 

C.    Standard calibration curve of Chlorthalidone:s

The standard calibration curve of chlorthalidone was obtained by plotting concentration (ppm) v/s absorbance using phosphate buffer pH 6.8 and phosphate buffer pH 7.4. (Fig.no 7)

 

Fig no. 7: Standard calibration curve of chlorthalidone in PBS pH 6.8 and pH 7.4

 

5.    EVALUATION OF CHLORTHALIDONE LOADED BUCCAL FILM:

1)    Physical appearance:

All films are transparent, smooth and elegant in appearance (Table no.5).

 

Table no. 5: Film characteristics of buccal film

 

Developed backing membrane was observed and checked for imperfectionswhich can be seen in table no 6 Image of optimized buccal film and backing membrane can be seen in figure no 8.

 

 

Fig No. 8: Developed buccal film, backing membrane and buccal film

 

Table no.6: Film characteristics of backing membrane

 

 

2)    Weight variation test:

The mean weight of all developed buccal films ranged from 89.3±1.5 to 124.6±1.52mg shown in table no. 7. The weight of each developed showed uniform weight distribution within each formulation.

 

3)    Thickness of films:

The mean thickness of all developed films ranged from 0.149±0.0015 mm to 0.211±0.0012 mm shown in table no. 7. F1 formulation showed highest thickness while F6 formulation showed lowest thickness.

 

4)    Folding endurance:

The mean folding endurance of all developed films ranged from 127±2.64 to 216.33±2.51 folds as shown in table no. 7. F1 formulation showed lowest folding endurance while F9 formulation showed highest folding endurance.

 

5)    Surface pH

The surface pH value was found to be between 6.5±0.2 as shown in table no. 7 which indicates the developed films are compatible and non-irritant to buccal mucosal surface.

 

6)    Drug content uniformity:

The drug content in buccal filmes was found to be between 84.0±0.06 % to 99.1±0.11% as shown in table no. 7.

 

7)    Swelling index:

Swelling behavior of all formulations was assessed. Swelling index of all formulation ranged from 11.2±4.05% to 33.9±6.77% as shown in table no. 8. Formulation F6 showed lowest swelling while formulation F2 showed maximum swelling.

 

8)    % moisture absorption:

The developed films were assessed to check the effect of humid conditions. The results ranged from 2.6±0.05% to 5.3±1.73% as shown in table no. 8.

 

9)    % moisture loss:

The moisture loss from developed films ranged from 1.03±0.01% to 2.8±1.60% as shown in table no. 8.

 

10)  Mucoadhesive strength:

The mucoadhesive strength of all formulation ranged from 4.5±0.05 gm to 8.3±0.15 gm as shown in table no. 8. As polymer concentration gets increased, the mucoadhesive strength of developed films also gets increased. It explained that F1 formulation having lowest polymer concentration (HPMC K4M 0.5% and HPMC E5 3%) showed minimum mucoadhesive strength and F2 formulation (HPMC K4M 2.5% and HPMC E5 5%) having highest polymer concentration showed maximum mucoadhesive strength.

 

11) Tensile strength:

The tensile strength of developed films ranged from 105.5±1.10 N/cm² to 247.4±4.53 N/cm² as shown in table no.8 which concluded that developed films had good mechanical strength. The formulation F1 showed lowest tensile strength while formulation F9 showed maximum tensile strength.

 

Table no. 7: Physical evaluation of chlorthalidone loaded buccal films

 

Table no. 8: Characteristics evaluation of chlorthalidone loaded buccal film

 

12) In-vitro drug release:

At the end of 8 hours, the cumulative drug release from developed films ranged from 92.2% to 98.9% as shown in fig no. 9. Formulation F8 showed highest drug release at the end of 8 hours while formulation F5 showed lowest drug release.

 

 

Fig no. 9: Comparison of in-vitro drug release profiles of formulation F1-F9

 

 

Table no 9 cumulative drug release of F2 in CD-14 apparatus

 

 

Fig no. 10: in-vitro drug release profiles of formulation F8 in CD-14

 

13) In-vitro drug release in CD-14 Dissolution apparatus:-

The optimized batch F8 was subject to in-vitro drug release in CD14 dissolution apparatus the result of the release of 6 batches is depicted in the figure 10 and table no 9 graph with the vessel 4 showing maximum release after 8 hours.

 

14) In-vitro diffusion studies:

The percent cumulative drug permeated for all formulation ranged from 88.6% to 92.8% as shown in fig no. 11. Formulation F1 with lowest polymer concentration showed maximum drug permeation while F9 with highest polymer concentration showed lowest drug permeation.

 

 

Fig no. 11: Comparison in-vitro drug diffusion profiles of formulation F1-F9

 

15) Drug release from backing membrane:

At the end of 8 hours, only 3% of drug was released from backing membrane as shown in fig no. 12. This indicates swelling of buccal film doesn’t affect much to integrity of ethyl cellulose backing membrane.

 

16) Ex-vivo permeation study:

As formulation F8 showed optimum mucoadhesive strength, tensile strength and, drug release profile etc. Thus F8 was selected for ex-vivo permeation study using porcine buccal mucosa. The cumulative drug permeated was found to be 87.2 ±0.93% as shown in fig no. 13.

 

 

Fig no. 12: in-vitro release from backing membrane of formulation B9

 

 

 

Fig no. 13: ex-vivo drug permeation profile of formulation F8

 

6.    DISCUSSIONS:

Films appeared to be smooth, transparent and uniform in texture. The pH of all formulations was within limits of the normal physiological pH range. The weight and thickness of all the films was found to be uniform. Folding endurance, mucoadhesive strength and tensile strength were in acceptable range. In vitro drug release studies at the end of 8 hours showed maximum release of about 98% and maximum drug permeation observed at the end of 8 hours was found to be 92.8%.

 

 

Formulations F1, F2, F9 and F8 showed swelling index between 11-18%. While formulation F8 showed least % moisture absorption (2.6±0.05%) and %moisture loss (0.8±0.015) which is good as buccal film should not gain more or loose moisture. F8 also showed optimum mucoadhesive strength 7.2±0.02 gm and optimum tensile strength i.e. 232.8±6.06 N/cm². The drug content of F8 formulation was also found to be optimum 95.4±0.06%. Thus formulation F8 is selected as optimum batch. Optimized formulation F8 showed good mucoadhesive strength, tensile strength and required in-vitro diffusion results.

 

Upto 40-50% of the drug was found to be released from the Buccal film within 1 hour and it is also permeated through the buccal mucosa as observed in ex vio experiments.

 

Further the drug concentration was maintained by slow release upto 95% and absorption through Buccal mucosa upto 8 hours.

 

Release from backing membrane was also studied to ensure the leaking of the drug from oral cavity. Drug permeation through goat mucosal membrane at the end of 8 hours minutes was found to be 85.89%.

 

7.    CONCLUSION:

This study concluded that mucoadhesive buccal film composed of chlorthalidone, HPMC polymers, SDC can be a potential formulation for management of hypertension. The formulation F8 is selected as optimized batch as it possessed the required physico-chemical properties, in-vitro drug release property and ex-vivo diffusion requirement for long-term release formulation for chlorthalidone. Mostly conventional formulations do not maintain the steady drug concentration. Therefore, by using buccal film, the steady drug concentration can be attained for long duration of time. It is observed that most of the time the heart condition is vulnerable at night or early morning hours. Chlorthalidone Buccal Film will provide overnight protection and help prevent the early morming heart attack. Hence, developed buccal film of chlorthalidone can prove to be best alternative to conventional formulations and can provide sustained release effect up to 8 hours.

 

8.    ACKNOWLEDGEMENT:

I deeply thank Dr Niraj Shah, CTX Life Sciences for providing me the drug as a gift sample for my project work. I also thank Colorcon Pvt. Ltd, Verna Goa for providing polymers as gift sample.

 

9.    CONFLICT OF INTEREST:

Authors declare no conflict of interests.

 

 

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Received on 19.03.2023         Modified on 20.06.2023

Accepted on 04.08.2023   ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Res. 2024; 14(1):15-24.