Freeze Dried Fenugreek Seed Mucilage as disintegrant for Fast Dissolving Tablets of Valsartan

 

Ashok A. Hajare*, Sumedha N. Kale, Trupti A. Powar

Bharati Vidyapeeth College of Pharmacy, Kolhapur, Maharashtra 416 013, India

Department of Pharmaceutical Technology, Bharati Vidyapeeth College of Pharmacy, Kolhapur- 416 013, Maharashtra, India

 

ABSTRACT:

The objective of the research work was to formulate fast dissolving tablet of valsartan using freeze-dried fenugreek seed mucilage as disintegrant. An attempt was made to extract the mucilage from fenugreek seeds and Ocimum tenuiflorum linn seeds and was evaluated for its various physicochemical characteristics. Fast dissolving tablets of valsartan was formulated by direct compression using different concentrations of fenugreek gum and Ocimum tenuiflorum gum as a natural superdisintegrants and compared with synthetic superdisintegrants like crospovidone. The tablets formulated using fenugreek gum and Ocimum tenuiflorum were evaluated for various physical tests like friability, weight variation, hardness. In vitro dissolution study showed 93.32% and 91.46% drug release, 42, and 53 seconds disintegration time, respectively for fenugreek and Ocimum tenuiflorum gum tablets. Natural gums like fenugreek and Ocimum tenuiflorum have better disintegration properties with improved disintegration time, when used in combination with synthetic disintegrants.

 

 

INTRODUCTION:

Oral routes of drug administration have wide acceptance up to 50-60% of total dosage forms available in the market. Solid dosage forms are the most popular forms due to ease of administration, highly versatile, accurate dosage and the patient compliance^[1]. Amongst them common solid dosage form preferred are capsule and tablet. An important drawback of oral dosage forms for some patients is the difficulty to swallow and readily access to water for easy swallowing dosage ^[2]. Dysphasia is common problem of all age groups, especially the geriatric, paediatrics, bedridden, nauseated, mentally retarded and uncooperative patients, due to physiological changes associated with these groups^[3]. In order to avoid this problem tablets, which rapidly dissolve or disintegrate in the oral cavity has attracted a great deal of attention.

 

Thus, fast dissolving drug delivery is rapidly gaining acceptance as an important new drug delivery technology, which enhances safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance^[4]. The fast dissolving tablet (FDT) has remarkable disintegration properties and it rapidly disintegrate without water in the oral cavity within few seconds. When an FDT is placed in the oral cavity, saliva quickly penetrates into the pores causing rapid disintegration^[5]. The primary benefit of the FDT is its improved patient compliance due to elimination of tablet swallowing as it is dispersed in the oral cavity. The other major benefits of FDT include accuracy of dosage, rapid onset of action, and increase in bioavailability^[6].

 

Valsartan is used in management of hypertension, as it is angiotensin II receptor antagonist. It is poorly water-soluble drug belonging to BCS Class III. Valsartan is a quickly absorbed when it administered orally but has very low systemic availability about 25%, which is further reduced to about 15% due to food- drug interaction. The drug is available commercially as conventional tablets 40, 80, and 160 mg. Trials were done to formulate valsartan as a transdermal dosage form to overcome its low. It is 95% protein bound and is mostly excreted as unchanged drug via bile ^[7]. Depending upon patient’s health its usual dose varies from 40 mg to 160 mg once daily. These dosages are reduced in conditions such as hepatic impairment, intravascular volume depletion, and renal impairment^. Fast dissolving tablets are one of the alternatives used to overcome bioavailability problems associated with conventional tablets. The drug is available commercially as conventional tablets 40, 80, and 160 mg ^[8].

 

Mostly, superdisintegrants are added to facilitate the break-up or disintegration of tablet or capsule content into smaller particles that can dissolve more rapidly than drugs in the absence of disintegrates. Many superdisintegrants like, croscarmellose sodium (Ac-di-sol), crospovidone and sodium starch glycolate (SSG) have been used in the formulations of FDTs. But they are more costly and toxic as compare to natural disintegrants. The natural disintegrants have proved to be safe, cheap and useful excipients with superior functionalities in the preparation of FDT’s. e. g. seed mucilage of Fenugreek^[9], Plantago ovata^[2], Ocimum tenuiflorum^[10], Hibiscus rosa sinesis linn^[11], Ocimum basilicum^[12], Lepidus sativum^[2], Tamarindus Indica polysachharide^[13], Cucurbita maxima pulp powder ^[14], a natural disintegrants in fast dissolving tablets. Fast dissolving tablet is a solid dosage form containing medicinal substance or active ingredient, which disintegrates rapidly usually within a matter of seconds when placed upon the tongue^[15].

 

Present study proposed to formulate an oral drug delivery of valsartan, in the form of FDTs by using direct compression method. The purpose of the present study was to extract the gum from fenugreek seeds and Ocimum tenuiflorum seeds. Further gum was evaluated for its powder flow properties (bulk density, tapped density, angle of repose, Carr’s index and Hausner’s ratio, swelling index, loss on drying and disintegration efficiency of fenugreek gum and Ocimum tenuiflorum gum is compared with widely used synthetic superdisintegrants viz. crospovidone in the formulation of FDTs. To assess efficiency of superdisintegrants, they were used in optimized concentration levels. The tablets were evaluated in various physical tests.

 

MATERIALS AND METHOD:

Materials:

Valsartan was purchased from Teva Pharmaceuticals, Verna, Goa, India. Seeds of fenugreek and Ocimum tenuiflorum were purchased from Kolhapur (India) local market and were authenticated from Shivaji University, Kolhapur. Microcrystalline cellulose (MCC), talc and magnesium stearate were purchased from Loba Chemie, Mumbai, and all other ingredients used throughout the study were of analytical grades.

 

METHODS:

Extraction and purification of fenugreek seed mucilage (FSM):

The extraction and purification of fenugreek seed mucilage were carried out with slight modifications. Accurately weighed 100g fenugreek seeds were grounded using laboratory mixer grinder. The fine powder was extracted by using boiling hexane in Soxhlet apparatus for 80 min. The obtained extract was treated with 95 %v/v ethanol (by maintaining its boiling) for 130 min in a conical flask to remove the unwanted saponins. Further enzyme deactivation was initiated by refluxing the extract with 70% v/v ethanol for 180 min. The resulting mixture was repeatedly treated with ethanol to remove undissolved traces. The residue was filtered through Whatman filter paper. The filtered residue was subjected to mechanical stirring at 700 rpm with addition of water for 8 h. The obtained mixture was centrifuged at 800 r. p. m. for 12 min at 10 °C. The supernatant contained crude fenugreek mucilage, which was precipitated by addition of 70 %v/v ethanol. The precipitated mucilage was washed with acetone, diethyl ether and water. The fenugreek mucilage obtained was considered pure and dried in oven at 45°C ^[9].

 

Extraction of Ocimum tenuiflorum seed mucilage (OSM):

The seeds of Ocimum tenuiflorum were blended and defatted by using petroleum ether as defatting agent in Soxhlet apparatus. Material was allowed to soak in distilled water for 12 h. after defatting. The swollen mass was spread and dried in an oven at 60°C. The dried mass was passed through sieve 30 and again through sieve 60 to obtain finer particle size. The mucilage so obtained was stored in desiccator until use ^[16].

 

Freeze drying of seed mucilage:

Seed mucilage of Fenugreek and Ocimum Tenuiflorum were freeze-dried using lyophilizer to improve their disintegration properties, whenever used as disintegrants in tablet dosage form. Suspensions of both seed mucilage’s and crospovidone were prepared separately using solvent as water: ethanol (8:2) and were freeze-dried using lyophilizer. The lyophilization cycle was adjusted by placing sample in deep freezer for pre-freezing at -40°C. The freezed sample were quickly allowed for primary drying in lyophilizer [Labconco, Model 117, A65312906] at 0.014 mBar pressure and -53°C temperature for 48 h. Secondary drying was carried out at 0.014 mBar pressure and 25 °C, respectively, for 2 h.

 

Physicochemical characterization of seed mucilage:

Organoleptic evaluation:

The isolated mucilage was characterized for organoleptic properties such as color, odor. The mucilage was weighed and dissolved in distilled water to obtain a 1 %w/v solution. The pH of solution was determined using digital pH meter.

 

Swelling index:

Accurately weighed 1 g of mucilage powder was taken in a 25 mL measuring cylinder, which was moistened with 0.5 mL of ethanol (95 %v/v). The final volume was adjusted to 25 mL of distilled water. The vessel was shaken vigorously for every 10 min for 1 h and was allowed to stand for 24 h. The volume occupied by the disintegrating agent including adhering mucilage was measured. The value of swelling index was calculated from the mean of three determinations ^[17].

 

Loss on drying:

To determine high levels of moisture or solvents present in the sample, loss on drying technique was used. The test samples were weighed (W₁) and heated in an oven for 2 h. It was then cooled in the dry atmosphere of desiccators and finally weighed (W₂) ^[9].

% Loss on drying= [(W₁ - W₂)/W₁] × 100                         (1)

Where,

W₁ = initial weight of the powder and

W₂ = final weight of the powder.

 

Drug-excipients compatibility studies:

The physicochemical compatibility between valsartan, fenugreek mucilage and Ocimum tenuiflorum mucilage used in the preparing FDTs were assessed by infrared spectral studies. FTIR analysis of isolated seed mucilage of fenugreek and Ocimum tenuiflorum was performed by FTIR Spectrophotometer [Alpha Brooker, Tokyo, Japan]. The samples were scanned under diffuse reflectance mold and the graph was plotted by KBr pellet method. The spectra were recorded in the 4000 to 400 cm^-1. The spectra of valsartan, fenugreek mucilage, and Ocimum tenuiflorum mucilage with optimized batches were compared ^[9].

 

Evaluation of powder blend:

The physical and mechanical properties of the lyophilized mucilage of fenugreek and Ocimum tenuiflorum seed such as bulk density; tapped density, angle of repose and the compressibility properties on the basis of Carr’s index and Hausner’s ratio were calculated and compared ^[9].

 

Preparation of fast dissolving tablets:

The valsartan FDTs (40 mg dose) were prepared by direct compression method, Table 1 and 2. The formulation contained varying proportions of fenugreek and Ocimum tenuiflorum seed mucilage along with the microcrystalline cellulose as direct compressible diluents and mannitol as sweetening agent, optimized best for FDT. The best batch of FDT containing fenugreek and Ocimum tenuiflorum seed mucilage were compared with synthetic superdisintegrant like crospovidone to determine their disintegration efficiency. All the ingredients were passed through sieve 60 separately to attain uniformity and mixed thoroughly. The blended mixture was directly compressible into tablets using KBr press ^[9].

 

Table1: Formula for fast disintegrating tablets using synthetics and natural disintegrants in different concentrations (data in mg)

 

Table 2: Formula for fast disintegrating tablets with optimized concentration of seed mucilage composite as superdisintegrant (data in mg)

 

Evaluation of tablets:

Tablets were evaluated for size, thickness, weight variation, friability, hardness, wetting time, disintegration time, drug content and in vitro dissolution study ^[19-20]. The thicknesses of the formulated tablets were measured by using Vernier callipers. The prepared tablets were tested for its weight uniformity. For the study, 20 tablets were weighed collectively and individually. From the collective weight, average weight was calculated. Each tablet’s weight was then compared with average weight to ascertain whether it was within permissible limits or not.

                (2)

 

The hardness of tablets was measured using Monsanto type hardness tester. Three tablets were selected from each formulation randomly and their hardness was measured. The mean ± SD values were calculated. Friability of the tablets was determined by using Roche friabilator. The weight of 20 tablets (initial weight) was subjected to friabilator at 25 revolutions per 4 min. Tablets were then dedusted, reweighed (final weight) and percentage loss was calculated ^[9]. Friability is obtained by the following formula:

                (3)

 

Wetting time and water absorption ratio:

A double folded tissue paper was placed in a petri dish and 6 mL water-soluble dye solution was added. A tablet was carefully placed on the surface of tissue paper. The time required for water to reach the upper surface of the tablet was noted as the wetting time. The wetted tablet was weighed and the water absorption ratio (R) was determined by using the equation: 

 

R = [(Wb - Wa)/Wb] × 100                                                (4)

Where, Wa and Wb are the weights of tablet before (dry weight) and after water absorption (wet weight), respectively.

 

Drug content:

Twenty tablets from different batches were weighed and powdered. The quantity of powder equivalent to 40 mg of valsartan was dissolved in pH 6.8 buffer solution and further diluted to 100 mL and was filtered and suitably diluted with the same solution. The drug content was estimated by UV spectroscopy at 250 nm.

 

Disintegration test:

A petridish was filled with 10 mL water. The tablet was carefully put at the centre of petri dish and the time was measured in seconds for complete disintegration of the tablet with no palpable mass remaining in the petri dish. The test was carried out in triplicate.

In -vitro dissolution studies:

Dissolution study was carried out by using USP Type II paddle dissolution apparatus, in 900 mL of artificial salivary solution (pH 6.8) at 37.0±0.5°C at 50 r. p. m. Aliquot of dissolution medium were withdrawn at regular time intervals and the same volume of, pre-warmed at 37.0 ± 0.5°C, fresh dissolution medium was replaced. The samples were filtered and drug content of valsartan in each sample was analyzed after suitable dilution by Shimadzu UV-spectrophotometer at 250 nm.

 

DSC analysis:

The DSC provides information regarding the physical properties like nature of the samples and degree of drug crystallinity. Thermal analyses of optimized formulation of both seed mucilage were recorded with DSC (SDT Q600 V8.2 Build 10). The temperature axis and cell constant were previously calibrated with Indium. A heating rate of 10^°C/min was employed over a temperature range of 10-350°C with nitrogen purging. The sample was weighed into an aluminium pan was used as reference. The peak area of melting endotherm was used for calculating heat of lyophilization techniques ^[21].

 

X-ray diffraction study:

Polymorphic changes in the drug are important since they might affect the dissolution rate and bioavailability. X-Ray diffraction spectra of optimized tablets of both seed mucilage were recorded on Philips Analytical XRD PW3710using Ni-filtered, CuKα-radiation, a voltage of 40 kV and a current of 25 mA. The instrument was operated in the continuous scan mode over a range of 10 to 70°C at step time of 0.5 sec ^[22].

 

Stability studies:

The stability studies of optimized tablets (F8 and F12) were performed as per ICH guidelines Q1C. The tablets for the study were sealed with aluminium packaging and kept in the humidity chamber maintained at 40 ± 2°C/75 % ± 5 % relative humidity (RH) and 25^°C/ 60 %RH for 6 months. Samples were withdrawn at each month and evaluated to investigate the changes ^[23].

 

RESULT AND DISCUSSION:

Physicochemical characterization of seed mucilage:

Fenugreek and Ocimum tenuiflorum seed mucilage were isolated and were identified. Loss on drying of both the mucilage was 2.5% and 4.6%, respectively. Swelling index, specific gravity and pH of both mucilage is presented in Table 3. Both isolated mucilage were soluble in hot water and swelled to form viscous solution in cold water and insoluble in acetone, ethyl alcohol, methanol and chloroform.

 

 

Table 3: Phytochemical properties of seed mucilage of fenugreek and Ocimum tenuiflorum

Test	Fenugreek seed mucilage	Ocimum seed mucilage
Organoleptic evaluation	Yellowish white, bitter smell	Brownish, no smell
pH	6.5	7.0
Swelling index	26 mL	28 mL
Loss on drying	2.5 %	4.6 %

 

Drug-excipients compatibility:

An FTIR spectrum of pure drug valsartan, optimized formulations F8 and F12 is presented in Fig. 1.  The powder samples were scanned at 4000 to 400 cm^–1. The peaks of valsartan at 2959.92 cm^-1 due to C-H stretching vibrations, 1470.67 cm^-1 due to C=O stretching vibrations and the bands associated with C-O stretching appeared at 1728.87 cm^-1. The characteristic unique absorption bands for valsartan were also seen at 756.67 cm^-1 and 1055.08 cm^-1. The optimized formulation F8 shows peaks at 2963.70 cm^-1 due to O-H stretching vibrations, 17328.87 cm^-1 due to C=O stretching vibrations and the bands associated with C-O stretching appeared at 1205.71 cm^-1. The characteristic unique absorption bands for formulation F8 were also seen at 1164.09 cm^-1 and 1598.75 cm^-1.

 

 

Figure 1: A FTIR spectrogram of pure valsartan (A), pure dried Ocimum tenuiflorum seed mucilage (B), pure dried fenugreek seed mucilage (C), F8 containing fenugreek seed mucilage (D), and F12 containing Ocimum tenuiflorum seed mucilage (E).

The optimized formulation F12 showed peak at 2965.09 cm^-1 due to C-H stretching vibrations, 1728.15cm^-1 due to C=O stretching vibrations and the bands associated with C-O stretching appeared at nearby 1206.03 cm^-1. The characteristic unique absorption bands for formulation F12 were also seen at 1053.99 cm^-1 and 1598.39 cm^-1. This characteristic FTIR peak of formulations F8 and F12 were retained. The mucilages peaks did not interfere with the peaks of drug confirming intactness and compatibility of the drug with them in the prepared formulations, indicating good stability.

 

Evaluation of powder blend:

Pre-compression studies:

The pre-compression characterization of mixed blend was performed to study mass volume relationship parameters. The blend was evaluated for bulk density, tapped density, Hauser’s ratio, compressibility index, angle of repose. The bulk density of mixed blend was found in the range of 0.4100±0.02 to 0.50±0.02 g/cm². The result indicated good packing capacity of tablets. The tapped density was found in the range of 0.47±0.02 to 0.59±0.08 g/cm². By using these two-density data, Hauser’s ratio and compressibility index was calculated. If the blend particle is more compressible then the powder will be more flowable and vice versa. The powder blend of all the formulations had Hausner’s ratio of 1.2 or less indicating the good flowability. The compressibility index was 14.12±0.2 to 17.40±0.08. Compressibility- flowability correlation data indicates a good flowability of powder blend. The flowability of powder was evidenced from better angle of repose. The angle of repose of powder blend was below 30° showing good to excellent flow properties with low friction occurring within the mass and better flow rate.  The results for the characterization of powder blend are presented in Table 4. The blend showed good flowability upon addition of 2% w/w talc as lubricant and 1% w/w magnesium stearate as glidant, respectively.

 

 

Table 4: Pre-Compression parameters of Valsartan FDTs at different superdisintegrant concentrations.

 

Evaluation of tablets:

The prepared tablets were evaluated for thickness, hardness, friability, weight variation, wetting time, disintegration time, and dissolution studies. The hardness and thickness studies indicated the mechanical strength of the tablet. The thickness of the tablet was 3.04±0.04 to 4.18±0.08 mm. The hardness of tablet varied from 4.80±0.2 to 5.65±0.06 kg/cm², which indicates satisfactory strength to withstand with the applied mechanical shocks. The average weight of prepared tablet was 2.25±0.02 to 3.44±0.14 mg. It was found that all the tablet formulations exhibited uniform weight with least standard deviation within the acceptable variation as per IP, Table 5. The friability of all the formulations was <1.0 %w/w indicating ability to withstand abrasion in handling, packaging and shipment with physical integrity. In case of content uniformity, the mean value and standard deviation of all the formulations were calculated and presented in Table 6. The result indicated uniform drug content complying specifications.

 

Table 5: Post compression parameters of Valsartan FDTs at different superdisintegrant concentrations.

 

Table 6: Post Compression Parameters of Valsartan FDTs at different superdisintegrant concentrations.

 

Wetting time and water absorption ratio:

The in-vitro wetting time was studied to know the time required for the complete wetting of tablet when placed upon tongue. The wetting time of all the formulations were 35±1.30 to 122±0.45 sec. Results suggest that wetting process was closely related to the inner structure of the tablets, especially pore size that affects water penetration into the tablets. Of all the formulations, the tablets formulated only with mucilage showed least wetting time, which had a direct impact on high water absorption ratio.

 

Disintegration test:

The disintegrant was incorporated in all the formulations to facilitate a disintegration of the tablet when it comes in contacts with water or saliva in mouth. Disintegrants drawing the water into the tablet leads to swelling and burst apart. In the formulation of fast dissolving tablet, the seed mucilage composites were used as disintegrant in different quantities. Tablet with 10 mg crospovidone disintegrated faster than tablets prepared with the seed mucilage. The disintegration time of all the formulations were found between 35±1.2 to 118±1.05 sec. The disintegrating properties of the superdisintegrants were depending upon their concentrations as the concentration of the disintegrants increased the time taken for the disintegration was reduced. The disintegration time was rapid in crospovidone compared to Fenugreek seed mucilage and Ocimum Tenuiflorum seed mucilage, respectively. It can be concluded that the disintegration process is fully depended on nature and concentration of superdisintegrants used.

In vitro dissolution study:

In-vitro dissolution study was carried out for FDT’s prepared using synthetic and natural disintegrants. Dissolution test was performed using dissolution test apparatus. The in-vitro percentage drug release studies on FDT formulations F5 – F8 within first 45 min was 79.28, 84.73, 88.78 and 93.32 %, respectively, Fig. 2. The in-vitro percentage drug release study for F9 – F12 formulations within first 45 min was 78.89, 82.65, 89.52 and 91.46 %, respectively, Fig. 3. The in-vitro percentage drug release of S1 and S2 formulations of FDTs within 45 min was found 93.20 and 94.86 %, respectively, Fig.4. The dissolution rate increased linearly with increasing concentration of superdisintegrants. Formulation S1 and S2 contained increasing quantity of synthetic disintegrant crospovidone, which shows 93.20 and 94.86% dug release within first 45 min. Formulation F5 to F8 contained increasing quantity of fenugreek seed mucilage and showed drug release 79.28%, 84.73%, 88.78%, 93.32%, respectively, within 45 min. Formulation F9 to F12 contained increasing quantity of Ocimum Tenuiflorum seed mucilage and showed 78.89%, 82.65%, 89.52%, 91.46% drug release, respectively within first 45 min. Overall percentage drug release was within 70-90% within in first 45 min. Formulations S2, F8 and F12 showed better drug release.

 

 

Figure 2: In vitro dissolution of Valsartan from FDTs containing different concentrations of crospovidone as a superdisintegrant (S1- 5 mg and S2- 10 mg)

 

 

Figure 3: In vitro dissolution of Valsartan from FDTs containing different concentrations of fenugreek seed mucilage composite as a superdisintegrant (F5- 2mg, F6-4mg, F7-6mg, and F8-8mg).

 

Figure 4: In vitro dissolution of Valsartan from FDTs containing different concentrations of Ocimum tenuiflorum seed mucilage composite as a superdisintegrant (F9- 2.5mg, F10-5mg, F11-7.5mg, and F12-10mg).

 

DSC thermal analysis:

DSC thermogram of pure drug valsartan, optimized batch F8 and F12 are presented in Fig. 5. Valsartan was characterized by a single, sharp melting endothermic at 105˚C whereas optimized formulation F8 showed at 171˚C and optimized formulation F12 showed no distinct melting endothermic for the drug. The disappearance of the melting endothermic of drug in the DSC thermograms of optimized formulations indicates that the drug is completely dissolved with excipients and is present partially in crystalline and partially distributed molecularly. There was lack of glass transition temperature in thermograms of any excipients and in FDTs.

 

Figure 5: A DSC thermogram of pure valsartan (A), pure dried Ocimum tenuiflorum seed mucilage (B), pure dried fenugreek seed mucilage (C), F8 containing fenugreek seed mucilage (D), and F12 containing Ocimum tenuiflorum seed mucilage (E).

X-ray diffraction study (XRD):

X-Ray diffraction spectra of valsartan, optimized formulations F8 and F12 is shown in Fig. 6. The XRD pattern of valsartan showed many intense and sharp diffraction peaks indicating its crystalline nature. Distinct intense peak of drug was found at 18˚, 19˚, 19˚, 20˚, 21˚, and 23˚. Crystallinity was determined by comparing same representative peaks heights in the diffraction patterns of the optimized formulation F8 and F12 prepared with drug. The absence of intense peaks in XRD pattern of both formulations indicates amorphous nature of drug and excipients. The reduced peak intensity indicates increased amorphous nature of drug and thus increased drug dissolution.

 

 

Figure 6: A XRD spectrogram of pure valsartan (A), pure dried Ocimum tenuiflorum seed mucilage (B), pure dried fenugreek seed mucilage (C), F8 containing fenugreek seed mucilage (D), and F12 containing Ocimum tenuiflorum seed mucilage (E).

 

Stability study:

Stability studies were carried out on optimized formulations F8 and F12 based on % cumulative drug release, disintegration time and wetting time obtained during formulation development. Formulations were stored at 25^°C/60%RH in stability chamber for period of 6 months ^[7]. The results for % cumulative drug release, disintegration time and wetting time showed no variations in any of the formulations. The results over a period of stability study indicated that formulation F8 and F12 were stable and retained their original properties, reported in Table 7 and 8.

 

Table 7: Post Compression Parameters of optimized F8 and F12 valsartan FDTs, before and after Storage at 25°C/60% relative humidity for 6 Months

 

Table 8: Percentage valsartan release of FDTs from optimized F8 and F12, before and after storage at 25°C/60% relative humidity for 6 Months

 

CONCLUSION:

Fast dissolving tablets of valsartan using freeze dried fenugreek and Ocimum tenuiflorum seed mucilage as a disintegrants were successfully prepared using direct compression method. The tablets were disintegrated within 52 seconds complying USFDA specifications. In-vitro dissolution study showed 98.41% drug release within first 45 min in artificial salivary medium (pH 6.8) showing significant improvement in dissolution. All the pre and post compression parameters were within the accepted limits. Stability study showed no variations in any parameters over the time. It can be concluded that fenugreek and Ocimum tenuiflorum seed mucilage could be used in freeze dried composite form to improve disintegration time of valsartan to minimize issues of low solubility and bioavailability. The easy availability, low cost and better process ability makes fenugreek seed mucilage a best alternative to synthetic disintegrants.

 

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Received on 14.12.2017            Modified on 24.12.2017

Accepted on 18.01.2018         © RJPT All right reserved