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Kumar et al: Formulation and In vivo Evaluation of Mucoadhesive Microspheres of Valsartan using Natural Gum 4393

Research Paper

Formulation and In vivo Evaluation of Mucoadhesive Microspheres of Valsartan using Natural Gum

Kota Ravi Kumar1*, D. V. R. N. Bhikshapathi2, and Gande Suresh3 1 Santhiram College of Pharmacy, N H - 40 Road, Nandyal- 518112, Andhra Pradesh, India; 1Research Scholar, Mewar University, Chittorgarh-312001, Rajasthan, India; 2Vijaya College of Pharmacy, Hayath Nagar, Hyderabad-501511, Telangana, India and 3Research Supervisor, Mewar University, Chittorgarh-312001, Rajasthan, India. Received November 05, 2018; accepted December 20, 2018

ABSTRACT Microspheres containing valsartan were prepared by the ionotropic gelation method, using sodium alginate with other mucoadhesive polymers namely HPMC K 100M and Eudragit RL 100, Olibanum gum and Guar gum. The prepared batches were evaluated for different evaluation parameters. The in vitro drug release of optimized formulation M13 showed the sustained release of Valsartan up to 98.89 ± 5.25% within 12 h whereas marketed product displayed the drug release of 90.99 ± 4.96%. The release mechanism from microspheres followed the zero order and higuchi model (R2 = 0.988, 0.979) respectively. The optimized formulation (M13) shown % entrapment efficiency, % yield, swelling index and mucoadhesiveness of 98.18, 97.64, 97.42 and 96.18% respectively. From FTIR studies no incompatibility was found between drug and excipients. SEM confirmed that particles were of spherical in shape. Optimized formulation (M 13) was stable at 40°C ±

2°C/75% RH ± 5% RH for 6 months. From in vivo bioavailability studies, valsartan optimized formulation M13 exhibited sustained release in a controlled manner when compared with marketed product. Mean time to reach peak drug concentration (Tmax) was 4.00 ± 0.05 h and 3.00 ± 0.04 h for the optimized and marketed product respectively, while mean maximum drug concentration (Cmax) was 10.85 ± 0.03 ng/mL and 8.54 ± 0.01 ng/mL respectively. AUC0–∞ of optimized formulation was found to be 147.42 ± 1.16 ng.h/mL, when compared with marketed product of 119.15 ± 1.13 ng.h/mL, AUC values of optimized formulation were found to be significantly higher (p<0.05) than of marketed product. Valsartan muco-adhesive microspheres would be a promising drug delivery system, could play a potentially significant role in pharmaceutical drug delivery in the treatment of hypertension.

KEYWORDS: Valsartan; Mucoadhesive microspheres; Ionotropic gelation method; In vivo bioavailability.

Introduction The most preferable route for the delivery of drugs is

oral route because easy administration and patient compliance (Malladi et al., 2016). Several gastro retentive delivery systems have been formulated to be retained in the gastric region for delayed time, it includes floating systems, high density systems etc. (Hooda et al., 2012). Mucoadhesion is the process by which a natural or a synthetic polymer can be adhered to the mucosal layer. Mucoadhesive polymers are water soluble and water insoluble polymers, which are swellable networks, jointed by crosslinking agents (Senthil et al., 2011). It has been a topic of interest in the design of drug delivery systems to prolong the residence time of the dosage form in gastrointestinal tract, which facilitates the intimate contact with the absorption surface to enhance the bioavailability of drugs (Robinson and Lee, 2005). The mucoadhesive property can help to delivering a drug for a prolonged period at a specific delivery site and offers several advantages over other oral controlled systems by

prolongation of residence of the drug in GIT (Mankala et al., 2011). Mucoadhesive microspheres become adhesive on hydration and hence used for localizing the drugs to a particular target site of gastrointestinal tract (GIT) for prolonged period of time (Bindu et al., 2010). Moreover, it is easy for administration, no patient compliances and flexibility in the formulation. One of the most feasible approaches for achieving a prolonged and predictable drug delivery in gastrointestinal tract (GIT) is to control gastro retentive drug delivery system which will provide important therapeutic options (Parmar et al., 2010). Valsartan is an angiotensin II receptor antagonist class of drug used for the treatment of hypertension, myocardial infarction and congestive heart failure. It treats the hypertension by blocking the vasoconstrictor and aldosterone secreting effect of angiotensin II selectively by blocking the binding of angiotensin II and angiotensin1 receptor in many tissues (Abdelbary et al., 2004). Valsartan drug was coming under BCS class III, low bioavaibility (approximately 20-

International Journal of Pharmaceutical Sciences and Nanotechnology

Volume 12 • Issue 1 • January – February 2019MS ID: IJPSN-11-05-18-KOTA

4393

4394 Int J Pharm Sci Nanotech Vol 12; Issue 1 • January− February 2019

25%), and shorter half-life (nearly 6 h). The treatment of anti-hypertension therapy needs long duration and to maintain plasma concentration the constant drug release due to overcome of toxic effects. It is aimed to design controlled delivery system of Valsartan for gradual release of drug in amounts sufficient to maintain therapeutic response for a specific period of time and to maintain dose frequency (Armstrong and James 1996).

Materials and Methods Materials

Valsartan was obtained as gift sample from MSN Laboratories Ltd, Hyderabad, India. Sodium alginate was purchased from Pruthvi Chemicals, Mumbai. Calcium chloride from SD Fine ltd, Mumbai. HPMC K 100M and Eudragit RL 100 were purchased from S. Kant. Health care ltd Vapi, Gujarat. Olibanum Gum and Guar gum was obtained from Rubicon Labs, Mumbai.

Methods Formulation of valsartan mucoadhesive microspheres Preparation of valsartan microspheres: The muco-

adhesive microspheres were prepared by using ionotropic gelation technique. In this method weighed quantity of Valsartan, HPMC K 100M and Eudragit RL 100 was added to 100 mL sodium alginate solution and thoroughly mixed at 500 rpm. Resultant solution was extruded drop wise with the help of syringe and needle into 100 mL aqueous calcium chloride solution and stirred at 100 rpm. After stirring for 30 min the obtained microspheres were washed with water and dried at 60oC for 4 h in a hot air oven and stored in desiccators (Table 1) (Das et al., 2004).

Evaluation studies of valsartan mucoadhesive microspheres: Particle size was determined using an optical microscope under regular polarized light (Trivedi et al., 2008). Angle of repose ( ) (Caroter et al., 1986), Bulk density, Tapped density (Haznedar et al., 2004), Compressibility index (Banker et al., 1989), Hausner’s ratio (Rockville et al., 1980), Swelling index (Rajput et al., 2010), Percentage yield (Kumar et al., 2011), Drug

entrapment efficiency (Pandya et al., 2011) were performed according to the reported methods (Figure 1).

Fig. 1. Mucoadhesive microspheres of valsartan.

Mucoadhesion study: The in vitro Mucoadhesive test was carried out using small intestine from chicken. The small intestinal tissue was excised and flushed with saline. Five-centimeter segment of jejunum were averted using a glass rod. Ligature was placed at both ends of the segment. 100 microspheres were scattered uniformly on the averted sac from the position of 2 cm above. Then the sac was suspended in a 50 mL tube containing 40 mL of saline by the wire, to immerse in the saline completely. The sac was incubated at 37oC and agitated horizontally. The sac was taken out of the medium after immersion for 1, 2, 3, 4, 5, 6, 7 and 8 h, immediately repositioned as before in a similar tube containing 40 mL of fresh saline and unbound microspheres were counted. The adhering percent was presented by the following equation (Ugwoke et al., 2005).

Mucoadhesion = (No. of microspheres adhered/ No. of microspheres applied) × 100

TABLE 1

Formulation trials for Valsartan mucoadhesive microspheres

Formulation code

valsartan (mg)

sodium alginate

HPMCK 100M (mg)

Eudragit RL 100 (mg)

Olibanm gum (mg)

guar gum(mg)

calcium chloride

M1 80 0.5 % 50 - 25 - 5 %

M2 80 1 % 100 - 50 - 5 % M3 80 1.5 % 150 - 75 - 5 % M4 80 2 % 200 - 100 - 5 % M5 80 2.5 % 250 - 125 - 5 % M6 80 3 % 300 - 150 - 5 % M7 80 3.5 % 350 - 175 - 5 % M8 80 0.5 % - 50 - 25 10% M9 80 1 % - 100 - 50 10%

M10 80 1.5 % - 150 - 75 10% M11 80 2 % - 200 - 100 10% M12 80 2.5 % - 250 - 125 10% M13 80 3 % - 300 - 150 10% M14 80 3.5 % - 350 - 175 10%


In vitro drug release studies: Release rate of drug from Mucoadhesive microspheres was carried out using USP dissolution apparatus. Accurately weighed number of microspheres from each batch was subjected to dissolution studies in triplicate manner. At appropriate intervals up to 12 h, specific volume of aliquots was withdrawn and analyzed spectrophotometrically at 249 nm. The withdrawn volume was replaced with an equivalent volume of fresh dissolution medium to maintain the volume of dissolution medium constant. The sample solutions were analyzed for the concentration of drug by UV spectrophotometer. The amount of drug released was calculated from the calibration curve of the same dissolution medium. (Sinha et al., 2004).

Kinetic modeling of drug release: In order to understand the kinetics and mechanism of drug release, the result of the in vitro dissolution study of microspheres were fitted with various kinetic equations like Zero order as cumulative percentage drug released vs time, first order as log percentage of drug remaining to be released vs time, Higuchi’s model cumulative percentage drug released vs square root of time. The r² and K values were calculated for the linear curves obtained by regression analysis of the above plots.

Drug excipient compatibility studies: The drug excipient compatibility studies were carried out by Fourier Transmission Infrared Spectroscopy (FTIR) method and Differential Scanning Colorimetry (DSC) method.

SEM studies: The surface and shape characteristics of pellets were determined by scanning electron microscopy (SEM) (HITACHI, S-3700N). Photographs were taken and recorded at suitable magnification.

Stability studies: The stability study of the optimized formulation was carried out under different conditions according to ICH guidelines. The optimized microspheres were stored in a stability chamber for stability studies (REMI make). Accelerated Stability studies were carried out at 40oC / 75 % RH for the best formulations for 6 months. The microspheres were characterized for the percentage yield, entrapment efficiency and cumulative % drug released during the stability study period.

In vivo Studies of Valsartan Animal preparation: Twelve New Zealand white

rabbits of either sex rabbits were (weighing 2-3 kg) selected for this study, all the animals were healthy during the period of the experiment. Animals were maintained at room temperature 25oC, RH 45% and 12 h alternate light and dark cycle with 100 % fresh air exchange in animal rooms, uninterrupted power and water supply and rabbits were fed with standard diet and water ad libitum. The protocol of animal study was approved by the institutional animal ethics committee bearing No: IAEC/1657/CMRCP/T2/Ph D-16/62.

In vivo Study design: Rabbits were randomly divided into two groups each group contains six animals. Group A rabbits were fed with Valsartan Mucoadhesive microspheres (optimized formulation M13), group B fed

with Marketed Product (0.5mg) product with equivalent dose to animal body weight. Blood samples (approximately 0.5 mL) were obtained with syringes by marginal ear vein at 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 20 and 24 h post dose. During collection, blood sample has been mixed thoroughly with heparin in order to prevent blood clotting. Plasma was separated by centrifugation of the blood at 5000 rpm in cooling centrifuge for 5 min and stored frozen at −20°C until analysis (Arifa and Basava, 2016). (Figure 2).

Fig. 2. Pictorial diagram showing mucoadhesive property of valsartan mucoadhesive microspheres in Chic Intestine.

Preparation of plasma samples for HPLC analysis: Rabbit plasma (0.5 mL) samples were prepared for chromatography by precipitating proteins with 2.5 mL of ice-cold absolute ethanol for each 0.5 mL of plasma. After centrifugation the ethanol was transferred into a clean tube. The precipitate was re suspended with 1 mL of acetonitrile by vortexing for 1 min. After centrifugation (5000 – 6000 rpm for 10 min), the acetonitrile was added to the ethanol and the organic mixture was taken to near dryness by a steam of nitrogen at room temperature. Samples were reconstituted in 200 μL of 70 % of acetonitrile and 30% water was injected for HPLC analysis.

Determination of valsartan in rabbit plasma by HPLC method: Determination of Valsartan (VAL) and internal standard Hydrochlorothiazide (HCT) by high performance liquid chromatography using a RP-C18 chromatographic column, Phenomenex Kinetex (150 mm × 4.6 mm i.d) and a mobile phase consisting of acetonitrile-phosphate buffer (0.05 M) with pH 2.8 in the proportion of (40/60, v/v) at a flow rate 0.8 mL/min and the wavelength detection was 227 nm. The retention time for HCT and VAL was 2.26, 11.19 min respectively (El-Gizawy et al., 2012).

Pharmacokinetic analysis: The pharmacokinetic parameters Cmax, Tmax, AUC and t1/2 were performed by a non- compartmental analysis using Win Nonlin 3.3® pharmacokinetic software (Pharsight Mountain View, CA USA). All values are expressed as the mean ± SD. Statistical analysis was performed with Graph Pad InStat software (version 3.00, Graph Pad Software, San


Diego, CA, USA) using one-way analysis of variance (ANOVA) followed by Tukey–Kramer multiple comparison test. Difference with p<0.05 was considered statistically significant.

Results and Disucssion Formulation of Mucoadhesive Microspheres

Mucoadhesive microspheres of Valsartan were formulated by ionotropic gelation method. Total 14 formulations were prepared using different polymers like sodium alginate, HPMC K 100 M, Eudragit RL 100 and calcium chloride in different concentrations. All the formulations were evaluated for their various physical parameters in Table 1.

Micromeretic Properties

The micromeretic properties parameters are shown in Table 2. All the formulations M1 to M14 varied from 60.19 ± 0.01 μm to 66.29 ± 0.05 μm. The formulation M13 shows the particle size 60.19 ± 0.01 μm. The bulk density and tapped density of all the formulations M1 to M14 were measured and they are ranged from 0.45±0.05 g/cc³ and 0.58 ± 0.06 g/cc³. Angle of repose of all the formulations was found satisfactory results. And the

formulation M13 was found to be 20.18˚±0.01 having good flow property.

The compressibility index values were found to be in the range of 10.49% to 16.23%. These findings indicated that the all batches of formulation exhibited good flow properties. The swelling of the formulation M13 was found to be 97.42%.

Mucoadhesion Study

All the 14 formulations of mucoadhesive microspheres were exposed to mucoadhesion test. The formulation M13 shows the high percentage of mucoadhesive property it shows 96.18% of adhesion nature. The percentage release and entrapment efficiency of all the formulations were measured by assay method. The mucoadhesive microspheres of formulation M13 shows the percentage yield 97.64%. The entrapment efficiency values of all the M13 formulation found to be 98.18% and are shown in Table 3.

In vitro Drug Release Studies

In vitro drug release studies were carried out and depicted in Figure 3 & 4. Among all the formulations M13 showed best drug release of 98.67% when compared with other formulations and marketed product was shown 90.99 ± 4.96 within 12 h.

TABLE 2

Micromeritic properties of formulated Valsartan mucoadhesive microspheres

Formulation code Particle size (μm) Bulk density (g/cc3) Tapped density (g/cc3) Angle of repose Carr’s index (%)

M1 61.19 ± 0.01 0.49 ± 0.07 0.59 ± 0.07 23.66˚ ± 0.02 14.33 M2 62.18 ± 0.01 0.46 ± 0.05 0.61 ± 0.01 22.18˚ ± 0.01 15.92 M3 63.11 ± 0.02 0.52 ± 0.01 0.60 ± 0.01 24.90 ˚ ± 0.03 16.23 M4 62.98 ± 0.01 0.51 ± 0.01 0.59 ± 0.07 23.67 ˚ ± 0.02 14.96 M5 63.67 ± 0.02 0.47 ± 0.06 0.63 ± 0.02 22.98 ˚ ± 0.01 15.98 M6 66.29 ± 0.05 0.49 ± 0.07 0.61 ± 0.01 23.31 ˚ ± 0.02 14.69 M7 64.98 ± 0.03 0.48 ± 0.06 0.59 ± 0.07 22.18 ˚ ± 0.01 13.66 M8 63.66 ± 0.02 0.51 ± 0.01 0.63 ± 0.02 26.68 ˚ ± 0.03 12.90 M9 62.23 ± 0.01 0.52 ±0.01 0.62 ± 0.01 25.66 ˚ ± 0.03 11.98

M10 61.18 ± 0.01 0.50 ± 0.01 0.59 ± 0.07 22.29 ˚ ± 0.01 13.59 M11 63.67 ± 0.02 0.48 ± 0.06 0.61 ± 0.01 24.67 ˚ ± 0.03 13.56 M12 62.44 ± 0.01 0.46 ± 0.05 0.60 ± 0.01 23.48 ˚ ± 0.02 12.24 M13 60.19 ± 0.01 0.45 ± 0.05 0.58 ± 0.06 20.18 ˚ ± 0.01 10.49 M14 61.23 ± 0.01 0.47 ± 0.06 0.59 ± 0.07 22.19 ˚ ± 0.01 11.27

TABLE 3

Percentage yield and entrapment efficiency of Valsartan Mucoadhesive microspheres Formulations

Formulation code Percentage Yield (%) Entrapment Efficiency (%) Swelling index (%) Mucoadhesiveness

M1 93.18 91.67 90.49 88.17 M2 94.68 92.14 91.63 89.78 M3 95.45 90.67 92.11 90.14 M4 96.66 91.24 90.23 93.67 M5 92.46 94.18 96.14 95.49 M6 91.89 93.67 95.63 93.98 M7 90.60 91.45 91.46 91.62 M8 93.45 92.86 93.48 92.47 M9 92.67 95.49 91.67 89.67

M10 91.68 96.67 92.18 90.18 M11 93.67 94.68 94.46 91.29 M12 92.44 92.44 96.37 93.26 M13 97.64 98.18 97.42 96.18 M14 95.17 96.23 95.13 95.16


Fig. 3. In-vitro cumulative % drug release of Valsartan Muco-adhesive microspheres.

Fig. 4. In-vitro cumulative % drug release of Valsartan mucoadhesive microspheres formulation.

Mathematical Modeling of Optimized Formula of Mucoadhesive Microspheres

In vitro dissolution has been recognised as an important element in drug development. Under certain conditions it can be used as a surrogate for the assessment of bioequivalence. There are several models to represent the drug dissoluton profiles where function of time is releated to the amout of drug dissolved from the pharmaceutical dosage systems.

In the view of establishment of release mechanism and quantitatively interpreting and translate mathe-matically the dissolution date being plotted.

From the results it is apparent that the regression coefficient value (0.988) closer to unity in case of zero order plot indicates that the drug release follows a zero-order mechanism. This data indicates a lesser amount of

linearity when plotted by the first order equation. Hence it can be concluded that the major mechanism of drug release follows zero order kinetics.

Further, the translation of the data from the dissolution studies suggested possibility of under-standing the mechanism of drug release by configuring the data in to various mathematical modeling such as Higuchi and Korsmeyer plots. The mass transfer with respect to square root of the time has been plotted, revealed a linear graph with regression value (0.979) close to one starting that the release from the matrix was through diffusion. Further the n value obtained from the Korsmeyer plots (0.512) suggest that the drug release from floating tablet was anomalous Non fickian diffusion. The data of optimized formulation and marketed product was shown in Table 4. (Figures 5,6,7,8)

TABLE 4

Release kinetics of optimized formulation of Valsartan mucoadhesive microspheres

Formulation Code

Zero Order First Order Higuchi Korsmeyer-Peppas R2 K R2 K R2 K R2 N

M13 0.988 6.487 0.690 0.130 0.979 27.149 0.932 0.512 Marketed product

0.947 5.861 0.627 0.111 0.910 25.981 0.954 0.568


Fig. 5. Zero order plots for the optimized Valsartan Mucoadhesive microspheres M13.

Fig. 6. First order plot for the optimized Valsartan Mucoadhesive microspheres M13.

Fig. 7. Higuchi plot for the optimized formulation of Valsartan Mucoadhesive microspheres M13.

Fig. 8. Korsmeyer-Peppas plot for the optimized formulation of Valsartan Mucoadhesive microspheres M13.

Drug Excipient Compatibility Studies FT-IR: From FTIR spectrums of Valsartan pure drug

(Figure 9), physical mixture (Figure 10) and optimized formulation (Figure 11), suggesting that there was no interaction between drug & excipients.

Fig. 9. FT-IR spectrum of pure drug valsartan.


Fig. 10. FT-IR spectrum of pure drug and other polymers.

Fig. 11. FT-IR spectrum of valsartan optimized formulation.

SEM of valsartan normal microspheres: The external and internal morphology of controlled release micro-spheres were studied by Scanning Electron Microscopy. Morphology of the various formulations of Valsartan microspheres prepared was found to be discrete and spherical in shape (Figure 12 & 13). The surface of the Valsartan microspheres was rough due to higher concentration of drug uniformly dispersed at the molecular level in the sodium alginate matrices. There are no crystals on surface which states that is drug is uniformly distributed.

Stability studies: Optimized formulation was selected for stability studies based on high cumulative % drug release. Stability studies were conducted for 6 months according to ICH guidelines. From these results it was concluded that, optimized formulation is stable and retained their original properties with minor differences.

In vivo bioavailability studies: Mean plasma concen-tration profiles of prepared Valsartan Optimized

formulation and marketed product are presented in Figure 14. All the pharmacokinetics parameters displayed in Table 5. The release pattern of both marketed and prepared formulation was not significantly different. The Cmax of test formulation and marketed formulations was 10.85 ± 0.03 ng/mL and 8.54 ± 0.01 ng/mL respectively. The Tmax of marketed formulation was 3.00 ± 0.04 h, and Valsartan optimized formulation was 4.00 ± 0.05 h. This delayed absorption of test and marketed preparation was most likely due to the sustained release of the drug. In order to estimate the amount of drug absorbed from the test formulation, the relative bioavailability was calculated from the AUC0–∞ of the marketed product and optimized formulation (119.15 ± 1.13 ng*h/mL for the reference product versus. 147.42 ± 1.16 ng. h/mL for the test formulation). The results indicated that the optimized formulation could increase the bioavailability of Valsartan effectively.


Fig. 12. Scanning electron micrographs of valsartan microspheres.

Fig. 13. Scanning electron micrographs of valsartan microspheres.

Fig. 14. Plasma concentrations at different time intervals for valsartan optimized formulation (M13) and Marketed Product.

TABLE 5

Comparison of pharmacokinetic parameters of Valsartan optimized formulation and Marketed Product

Parameters Valsartan Optimized

formulation Marketed Product

Cmax(ng/mL) 10.85 ± 0.03 8.54 ± 0.01 AUC0-t(ng. h/mL) 120.15 ± 1.12 103.21 ± 1.26 AUC0-∞ (ng. h/mL) 147.42 ±1.16 119.15 ± 1.13 Tmax (h) 4.00 ± 0. 05 3.00 ± 0.04 t1/2 (h) 8.85 ± 0.41 6.91 ± 0.01

Conclusions

In the present investigation, stable valsartan gastroretentive mucoadhesive microspheres were prepared by ionotropic gelation method. The results revealed that the sodium alginate, HPMC K 100M and Eudragit RL 100, Olibanum gum, Guar gum and calcium chloride considerably affected the drug entrapment efficiency, particle size, % yield, and % mucoadhesion.


The optimized formulation (M13) was found to be efficient, % yield (97.64%), entrapment efficiency (98.18%), swelling index (97.42%) and mucoadhesion (96.18%). The mucoadhesive property facilitates the microspheres to adhere to the gastric mucosal surface and reside in stomach for prolonged time which eventually leads to better bioavailability. Cumulative % drug release studies showed sustained drug release up to 98.67 ± 5.25% (12 h). Drug release from valsartan microspheres followed zero order and Higuchi model suggested that it followed the diffusion-controlled mechanism. The FTIR studies displayed that drug and excipients were compatible. SEM results revealed that the prepared microspheres were spherical in shape. The stability of optimized formulation (M13) was studied as per ICH guidelines and found stable for 6 months. From in vivo bioavailability studies, valsartan optimized formulation M13 exhibited sustained release in a controlled manner when compared with marketed product. Mean time to reach peak drug concentration (Tmax) was 4.00±0.05 h and 3.00±0.04 h for the optimized and marketed product respectively, while mean maximum drug concentration (Cmax) was 10.85±0.03 ng/mL and 8.54±0.01 ng/mL, respectively. AUC0–∞ of optimized formulation was found to be 147.42±1.16 ng*h/mL when compared with marketed product of 119.15±1.13 ng*h/mL. AUC values of optimized formulation were found to be significantly higher (p<0.05) than of marketed product. Valsartan mucoadhesive microspheres would be a promising drug delivery system, could play a potentially significant role in pharmaceutical drug delivery in the treatment of hypertension. Based on these studies, Valsartan mucoadhesive microspheres appear to be a highly promising with prolonged release in a controlled manner with higher bioavailability in the efficient management of hypertension.

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Address correspondence to: Ravi Kumar Kota, Santhiram College of Pharmacy, N H - 40 Road, Nandyal- 518112, Andhra Pradesh, India. Mob: 9704129298 E-mail: [email protected]

January – February 2019 Research Paper MS ID: IJPSN-11-05 ...ijpsnonline.com/Issues/4393.pdf ·...

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Transcript of January – February 2019 Research Paper MS ID: IJPSN-11-05 ...ijpsnonline.com/Issues/4393.pdf ·...