INTRODUCTION:

The primary goal behind development of drug delivery carrier is to target a drug directly to its site of action to obtain a better therapeutic effect¹. Oral route persist the route of choice due to the ease of dose administration and patient compliance. Oral route of drug administration offers various advantages for administration of drugs used to deliver drugs to act locally to the gastrointestinal tract. Development of oral drug delivery systems has various benefits like low cost, flexible formulation approach, drug delivery for a long time period and improved bioavailability².

Oral pharmaceutical formulations are classified into two classes namely conventional and modified release systems. Conventional release systems are designated to disintegrate quickly, and allow drug release in a short time. The main limitation of such conventional system is fluctuations in drug concentration in blood plasma, which cause reduced or loss in intended therapeutic effects or increased frequency of side effects. In case when the drug concentration decreased due to its metabolism and excretion, administration of multiple dosages in a day is needed.

Tablets are the most conventional and economic pharmaceutical formulations prepared to release the medicament after oral administration. Time and cost effectiveness make tablets still the favoured dosage forms. The performance of tablet depends on its matrix and surface properties, which govern the mechanical and chemical properties of tablet. Conventional release tablets result in relatively increased number of dosages. These conventional tablets may show more fluctuations in plasma drug concentration. To avoid the fast sub-therapeutics level of the drug another dose is usually given for treating chronic diseased conditions³.

To overcome the limitation of conventional tablets, development of various modified release drug products is gaining more attention to control the drug release. Modified release products use polymers to alter the rate of drug release under controlled pH conditions of gastrointestinal tract (g.i.t). The term controlled-release was originally used to depict various extended release formulations such as prolonged action, sustained-release, slow-release, long-action and programmed delivery. The basic rational of controlled or sustained release formulation is to control drug at target site, avoiding the frequent dosing and improve efficacy effect of a drugs by altering its pharmacokinetics and pharmacodynamic profile^4,5,6.

However, such controlled delivery systems extend limited advantages for bioactives having narrow therapeutic window. Various drugs such as gliclazide and pioglitazone are absorbed from duodenum and jejunum⁷. However, limited absorption may be possible at these sites due to the quick passage of dosage form (about 1-2 h)^8-11. To meliorate the oral availability of these therapeutics, the retention time of the delivery system need to be extended in the stomach, so that the drug will be available in the solution form when it reached to the area from where its maximum absorption is possible¹². This can be successfully accomplished by developing gastroretentive controlled release carrier that can resist the grinding, crushing, contractions, and peristaltic movements and allow prolonged drug release^13-15. Retention for prolonged period of time leads to improved oral bioavailability, and clinical efficacy, also reduces the number of dosage administration and improves patient compliance¹⁶. Hence, extended release drug delivery systems with gastric retention are recommended as potential delivery systems for effective drug delivery¹⁷.

Absorption of lisinopril is slow, variably, and incomplete (~30%) after oral administration. To overcome this limitation of lisinopril, the present study was designed to develop floating gastroretentive tablets by wet granulation technique.

MATERIAL AND METHODS:

Materials:

Lisinopril was received as gift sample from Wockhardt Ltd., Mumbai, India. Crosprovidone and Croscarmellose sodium were received as gift sample from Signet Chemicals, Mumbai, India. HPMC K4 M and Carbopol 934 P were purchased from Sigma Aldrich Chemicals, Bangalore. Lactose, polyvinylpyrrolidone (PVP), sodium bicarbonate, citric acid and magnesium stearate were purchased from Fines, Mumbai, India.

Methods:

Preparation of granules for tablet formulation:

Accurately weighed amount of lisinopril was mixed in a clean and dry mortar with all ingredients except magnesium stearate (Table 1 and 2). The powder was blended well for 10 min. PVP-K30 solution in 5% w/v isopropyl alcohol was used for wet granulation. It was passed through sieve # 20 and dried at 40°C in a hot air oven. Lubricated of the dried granules was carried using magnesium stearate.

Micromeretic characterization of granules:

Determination of bulk density and tapped density:

Pre-weighed granules were placed in a 10 mL measuring cylinder. The initial volume was recorded. The cylinder containing granules was tapped 100 times. The density determinations were calculated using below formula¹⁸:

Weight of Granules

Bulk Density =-------------------------------------

Initial Volume

Determination of Hausner’s ratio:

The density findings of the granules were utilized to calculate Hausner’s ratio using below formula¹⁸:

Tapped Density

Hausner’s ratio =-------------------------------------

Bulk Density

Determination of Carr’s index:

The density (bulk and tapped) results were utilized to calculate Carr’s index by below formula¹⁸:

Tapped Density - Bulk Density

Carr’s index (%) =-------------------------------------

Tapped Density

Table 1: Composition of sustained release gastroretentive floating tablets of Lisinopril.

Ingredients (mg/tablet)	LFT₁	LFT₂	LFT₃	LFT₄	LFT₅	LFT₆	LFT₇	LFT₈	LFT₉	LFT₁₀	LFT₁₁
Lisinopril	20	20	20	20	20	20	20	20	20	20	20
HPMC K4 M	100	90	100	50	40	100	50	55	90	100	50
Carbopol 934 P	-	20	30	30	50	80	30	50	50	60	40
Crosprovidone	4	-	-	-	3	2	-	2	-	-	-
Croscarmellose sodium	-	-	3	2	-	-	2	-	-	-	4
Lactose	91	78	48	99	95	13	113	81	41	35	94
PVP (% w/v)	5	5	5	5	5	5	5	5	5	5	5
Sodium bicarbonate	45	50	55	55	50	45	45	50	55	45	50
Citric acid	8	10	12	12	10	8	8	10	12	8	10
Magnesium stearate	7	7	7	7	7	7	7	7	7	7	7

Determination of angle of repose:

The granules were allowed to pass freely through a fixed funnel (lower tip at 2cm above the surface). The granules were poured until the tip of pile touched funnel. The tan-1 was calculated using pile height and radius of its base ratio as per the below formula¹⁸:

tan^-1 = h/ r

Where, h is the height of the pile and r is the radius of pile base

Formulation of floating tablets containing lisinopril:

The granules were compressed into tablets by wet granulation method using 9mm diameter die cavity and flat faced punches in a rotary tablet press (Rolax manual tablet compression machine, Ambala, India). The composition of controlled release gastroretentive floating tablets of lisinopril is given in Table 1 and 2. The weight of tablets was adjusted to 270mg¹⁹.

Evaluation of tablets:

Determination of weight variation:

For the determination of tablet weight variation, USP procedure for uniformity of weight was followed. Briefly, 20 tablets were taken randomly from each batch and the weight was recorded individually and collectively using a calibrated weighing balance. The average tablet weight was used to estimate tablet weight variation.

Determination of tablet hardness:

Ten tablets were taken randomly from each batch and tested for hardness by Monsanto tablet hardness tester.

Determination of tablet thickness:

Ten tablets were randomly taken from each batch and tested for thickness using vernier caliper.

Determination of friability:

From each batch, twenty tablets were initially weighed and placed in the chamber of a USP friability tester (Electrolab EF-2 friabilator). The friabilator was operated at 25rpm for 100 revolutions. After 100 revolutions, the tablets were collected, de-dusted and re-weighed. The percentage friability was calculated using below formula:

Initial weight - Final weight

Friability (%) = ------------------------------------- X 100

Initial weight

Determination of drug content:

It was estimated by crushing 6 tablets from each batch. The tablet powder (≡ average tablet weight) was taken in 100mL of 0.1N HCl and stirred for 24 h. After 24 h, the mixture was filtered through Whatman filter papers. The filtrate was diluted suitably and analyzed spectrophotometrically at 206nm.

Swelling studies:

The swelling of tablet was examined in petri plate containing 0.1 N HCl, pH 1.2. At predetermined intervals, the tablet was taken out from the petri plate and the percentage swelling was determined using below formula:

Weight of the swollen tablet -Initial weight of tablet

Swelling (%)= ------------------------------------ X 100

Initial weight of tablet

Determination of in vitro buoyancy:

The floating lag time and floating duration were determined by placing 3 tablets from each batch in 100 mL 0.1N HCl (pH 1.2) and allowed to float. The floating lag time was determined on the basis of time taken by the tablet to float at the top of the media constantly for a long time. The floating duration was determined on the basis to recording the total time period for which the tablet floated constantly.

In vitro release study:

The release of lisinopril was investigated using USP tablet dissolution apparatus type - II (DS 8000, Lab India, Mumbai, India). The dissolution experiments were done in 900mL 0.1N HCl (pH 1.2) at 100 rpm and 37±0.5°C. Five milliliter sample was taken at of every 15 min for first hour followed by 1 hour for first 4 hour and by every 2 hour interval till 8th hour. Sink condition was maintain by adding same amount of buffer after each sampling added to. The samples were diluted sufficiently and analyzed using a UV spectrophotometer (1700, Shimadzu, Japan) at 206nm. Each sampling time was done in triplicate.

RESULTS AND DISCUSSION:

Micromeritic characterization of granules:

Bulk density:

The bulk density was observed in the range of 0.459 to 0.564g/mL (Table 2). The results confirmed that the obtained bulk densities were almost similar for all batches indicating almost identical flow behavior and packing arrangement of particles.

Tapped density:

The results of tapped density are shown in Table 2. The tapped density was recorded in the range of 0.567 to 0.623g/mL. The results indicating very small or no difference in granule volume even after 100 tapping which shows almost similar flow properties.

Hausner’s ratio:

It also indicates flow properties of the granular mass. In the present study, the value of Hausner’s ratio was from 1.083 to 1.910 (Table 2), indicating good flow of granules. However, formulation LFT4, LFT8, LFT4, LFT11 had Hausner’s ratio value > 1.25 indicating poor flow.

Carr’s index:

It is suggested that the value of Carr’s index in the range of 5 to 15 indicates excellent and from 15 to 20 indicates good flow of material. On the other side, the value < 30 indicates cohesiveness of particles with poor flow. The value of Carr’s index was observed from 7.692 – 40.444 indicating excellent to very poor flow properties (Table 2).

Angle of repose:

It was determined to estimate flow behavior of granules. The angle of repose for all the formulations was ranged from 24.17 – 27.61 (Table 2), which indicates good flow of granular and indicating it was non-aggregating.

Evaluation of floating tablets:

Weight variation:

The average weight of the tablet was found in the range of 281.384mg to 278.616mg (Table 3). The maximum percentage deviation was found to be 1.384. None of the batch shows a deviation of more than ± 7.5% (Indian Pharmacopoeial limit). The results conclude that the tablets complied with weight variation test.

Tablet hardness:

The hardness for different batches was found between 3.6±0.120 to 4.2±0.521kg/cm2 showing satisfactory mechanical strength (Table 3).

Tablet thickness:

The maximum average thickness from all the formulations was 1.32 mm. The minimum average thickness from all the formulations was 1.09 mm. The average thickness from all the formulations was 1.14 mm. The percentage deviation in thickness was found to be 0.02 to 0.18.

Friability test:

The friability loss was less than 1% in all the formulations (0.19±0.082% to 0.82±0.170) (Table 3).

Table 2. Micrometric properties of granules (Formulation LFT₁-LFT₁₁).

Micrometric property	Formulation code
Micrometric property	LFT₁	LFT₂	LFT₃	LFT₄	LFT₅	LFT₆	LFT₇	LFT₈	LFT₉	LFT₁₀	LFT₁₁
Bulk density (g/mL) ± SD	0.505 ± 0.15	0.511 ± 0.24	0.464 ± 0.61	0.513 ± 0.09	0.534 ± 0.11	0.508± 0.43	0.564 ± 0.37	0.487 ± 0.09	0.514 ± 0.61	0.512 ± 0.31	0.459 ± 0.22
Tapped density (g/mL) ± SD	0.587 ± 0.34	0.567 ± 0.27	0.615 ± 0.51	0.611 ± 0.54	0.598 ± 0.21	0.608 ± 0.22	0.611 ± 0.17	0.623 ± 0.81	0.584 ± 0.52	0.612 ± 0.27	0.609 ± 0.22
Angle of repose (θ) ± SD	24.17 ± 0.51	26.11 ± 0.41	27.61 ± 0.34	26.27 ± 0.31	24.97 ± 0.72	26.31 ± 0.41	24.43 ± 0.42	26.00 ± 0.34	27.81 ± 0.21	25.90 ± 0.17	25.47 ± 0.48
Hausner’s ratio	1.162 ± 0.10	1.109 ± 0.12	1.325 ± 0.34	1.910 ± 0.22	1.119 ± 0.31	1.196 ± 0.22	1.083 ± 0.21	1.270 ± 0.34	1.136 ± 0.31	1.195 ± 0.22	1.326 ± 0.35
Carr’s Index (%) ± SD	13.969 ± 2.19	9.876 ± 1.05	24.552 ± 2.31	16.039 ± 0.94	10.702 ± 0.28	16.447 ± 0.64	7.692 ± 0.52	21.829 ± 1.02	11.986 ± 1.23	16.339 ± 2.17	40.444 ± 1.34
Drug content (%) ± SD	96.15 ± 1.37	92.02 ± 0.82	96.11 ± 2.34	98.14 ± 2.37	99.04 ± 1.81	99.11 ± 1.34	95.27 ± 1.38	97.13 ± 1.62	96.34 ± 2.72	98.37 ± 1.92	99.04 ± 1.63

Table 3. Various evaluation parameters of developed floating tablets of lisinopril.

Formulation code	Hardness (kg/cm²)	Friability (%)	Weight uniformity (mg)	Drug content (mg)
LFT₁	3.6 ± 0.120	0.61 ± 0.131	280 ± 1.028	99.11 ± 1.34
LFT₂	3.9 ± 0.620	0.55 ± 0.108	280 ± 1.067	99.04 ± 1.81
LFT₃	3.6 ± 0.130	0.37 ± 0.100	280 ± 0.987	98.14 ± 2.37
LFT₄	4.1 ± 0.110	0.82 ± 0.170	280 ± 1.027	96.11 ± 2.34
LFT₅	3.4 ± 0.550	0.19 ± 0.082	280 ± 0.982	92.02 ± 0.82
LFT₆	3.9 ± 0.076	0.27 ± 0.055	280 ± 1.384	96.15 ± 1.37
LFT₇	4.1 ± 0.225	0.62 ± 0.071	280 ± 1.327	99.04 ± 1.63
LFT₈	4.2 ± 0.521	0.62 ± 0.082	280 ± 0.972	98.37 ± 1.92
LFT₉	4.1 ± 0.132	0.37 ± 0.061	280 ± 1.368	96.34 ± 2.72
LFT₁₀	3.9 ± 0.521	0.52 ± 0.052	280 ± 1.357	97.13 ± 1.62
LFT₁₁	3.7 ± 0.214	0.36 ± 0.105	280 ± 1.270	95.27 ± 1.38

Drug content:

The maximum and minimum percentage drug content was found to be 100.18% and 96.64%, respectively (Table 3). The limit is within the specified pharmacopoeial specification (IP i.e. ±10). The results of drug content study were complying pharmacopoeial specifications.

Swelling studies:

Water uptake approach was used to determine swelling behavior of prepared tablets. Due to the simultaneous swelling of polymer matrix and continuous dissolution of drug into bulk the strength of matrix gets reduced. However, swelling may also lead to sustain the rate of drug release because of the increase in diffusional path. In the present study, maximum swelling was recorded after 8 hour (Table 4). Highest percent swelling was ascertained at the end of 8 hour (Figure 1). Percentage swelling was increased with an increase in polymer concentration.

All the tablets had similar hydration behaviour, as they reached a plateau after 8 hour and remained unchanged until 12 hour. Almost all the formulations reached > 45% hydration. High water uptake capacity of the tablets may be due to the quick hydration of polymers and swelling rate of the tablets increased with an increase in polymers concentration.

Figure 1. Swelling behavior of lisinopril floating tablet in 0.1 N HCl, 1 h (A), 2 h (B), 4 h (C), 8 h (D), and after 12 h (E).

Table 4. Results of percentage hydration.

Formulation code	Hydration (%)
Formulation code	1 h	2 h	4 h	8 h	12 h
LFT₁	48.92	51.86	68.32	71.12	72.05
LFT₂	46.41	50.76	56.31	64.91	65.37
LFT₃	47.82	53.33	68.34	83.51	84.32
LFT₄	50.26	62.79	75.61	90.21	91.10
LFT₅	48.69	58.21	74.58	88.96	89.08
LFT₆	53.51	59.36	73.11	90.61	91.05
LFT₇	49.14	67.87	71.51	84.12	94.31
LFT₈	44.55	65.23	72.87	86.37	86.92
LFT₉	49.34	62.54	73.95	81.06	81.67
LFT₁₀	52.22	52.35	67.36	80.01	81.12
LFT₁₁	54.94	54.35	68.04	81.17	81.52

Determination of buoyancy:

The optimum floatation (less lag time and more total floatation) was observed at 55 mg/ tablet of sodium bi-carbonate so this was considered as optimized level of gas forming agent. The tablets with HPMC exhibited short buoyancy lag time and remained buoyant for longer duration than the tablets containing carbopol. The percentage buoyancy of all the formulations was found to be good (Figure 2). The floating lag time varied from 22.9 sec to 68.6 sec depending on polymer type and concentration (Table 5).

Table 5. Various evaluation parameters of developed floating tablets of lisinopril.

Formulation code	Floating lag time (s)	Total floating time (h)
LFT₁	34.3 ± 3.0	12.0 ± 2.5
LFT₂	38.0 ± 5.0	16.0 ± 1.5
LFT₃	22.2 ± 4.0	20.0 ± 1.5
LFT₄	25.1 ± 6.0	18.0 ± 1.4
LFT₅	22.9 ± 4.0	20.0 ± 1.0
LFT₆	68.6 ± 3.0	12.0 ± 0.5
LFT₇	67.0 ± 2.0	16.0 ± 1.0
LFT₈	51.7 ± 3.0	12.0 ± 2.0
LFT₉	23.0 ± 2.0	20.0 ± 0.5
LFT₁₀	67.5 ± 4.0	13.0 ± 0.5
LFT₁₁	49.3 ± 2.0	16.4 ± 1.0

Figure 5.7 Buoyancy sequence of lisinopril floating tablet in 0.1 N HCl, at (A) 0 sec, (B) 5 sec, (C) 10 sec, (D) 12 sec, (E) 4 h, and (F) after 18 h.

In-vitro dissolution studies:

Release of drug from the tablets changed depending on the type and ratio of matrix-forming polymer. HPMC and Carbopol had excellent gelling properties, and also helped in sustaining effect. The in-vitro drug release profile of tablets containing Carbopol 934P with HPMC K4M showed sustained drug release profile (Figure 3 and Figure 4). On physical examination of tablets during dissolution study, it was observed that the tablets were swollen over the period of time.

Figure 3. Dissolution profile of Lisinopril from floating matrix tablets (formulation LFT₁ to LFT₅). All values are expressed as mean± SD, n=3.

The in-vitro drug release profile of tablets containing crosprovidone at its higher level and HPMC alone showed more than 50% of cumulative percentage drug release at the end of first 4 h of the dissolution study. However, from these tablets, at the end of 8 h the cumulative percentage drug release was found to be 71.03 ± 4.975%. Formulations F11 containing HPMC K4M and Carbopol 934 (50:40 ratio) and higher level of Croscarmellose sodium (4 mg) showed a higher percentage of drug release (79.15 ± 2.688%) when compared to the other formulations. HPMC K4M alone could not have prolonged sustaining effect. However, formulations containing HPMC K4M at its higher level in combination with Carbopol has shown more sustaining effect.

Figure 4. Dissolution profile of Lisinopril from floating matrix tablets (formulation LFT₆ to LFT₁₁). All values are expressed as mean± SD, n=3.

The drug release profile form the prepared floating tablets could be attributed to the increased hydration and increased swelling behaviour of polymer. The higher swelling of polymer may increase the diffusional path-length to allow drug to diffuse out.

Kinetic treatment to dissolution data:

Various mathematical models such as zero order, first order kinetics, Higuchi’s equation, and Peppas’ equation have been established that could explain exactly which type of drug release kinetics and mechanism followed. In case of first order plot, the in vitro release data was plotted as log cumulative percentage remaining to release against time. For Higuchi’s plot, a plot of percentage cumulative drug released against square root of time was plotted.

For Peppas’ plot, a plot of log percentage cumulative drug released against log time was plotted. The type of drug release kinetics and mechanism was confirmed based on the values of r² values. The results suggested that the drug release from the floating tablets followed first order kinetics and Higuchi’s equation (highest r² coefficients) (Table 6). Higuchi’s plots were found to be linear in all the formulations indicating diffusion controlled release from all the floating tablets. The release exponent “n” was in the range more than 0.5 and less than 1 for Peppas’ plots, confirming drug release via diffusion with swelling. Similar kind of drug release kinetic and mechanism has been reported earlie^20-22.

Table 6. Results of drug release kinetic studies.

Formulation code	Zero order (r²)	First order (r²)	Higuchi’s model (r²)	Peppas’ model (r²)
Formulation code	Zero order (r²)	First order (r²)	Higuchi’s model (r²)	r²	n
LFT₁	0.9005	0.9709	0.9760	0.9718	0.5117
LFT₂	0.9093	0.9620	0.9962	0.9844	0.5613
LFT₃	0.9119	0.9618	0.9855	0.9869	0.5346
LFT₄	0.9051	0.9588	0. 9838	0.9839	0.5133
LFT₅	0.9162	0.9736	0.9891	0.9897	0.5234
LFT₆	0.9179	0.9499	0.9956	0.9752	0.5157
LFT₇	0.9034	0.9709	0.9959	0.9915	0.5057
LFT₈	0.9143	0.9943	0.9920	0.9902	0.5492
LFT₉	0.9035	0.9429	0.9732	0.9831	0.5192
LFT₁₀	0.9011	0.9472	0.9946	0.9917	0.5330
LFT₁₁	0.9094	0.9739	0.9827	0.9787	0.5976

CONCLUSION:

Sustained release floating gastroretentive tablets of lisinopril were successfully prepared by wet granulation technique. The study was conducted to assess the effect of polymer type and concentration on matrix characteristics such as buoyancy behavior and release profiles. The type and quantity of polymer played main role for providing buoyancy and sustained release profile. As the concentration of polymer increases, lag time also increase. It was observed that the prepared tablets had ideal properties to be used as gastroretentive system. The developed floating system enhanced the retention time and prolonged the drug release in the stomach, which, in turn, improved the local availability of the drug. Overall, a floating system for lisinopril was formulated successfully with less buoyancy lag time, long buoyancy time and sustained drug release rate from the hydrophilic matrices. The tablets are anticipated to provide a new choice of safe product with better bioavailability for the treatment of high blood pressure (hypertension).

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

REFERENCES:

1. Shivakumar HG, Gauda VD. Floating control drug delivery systems for prolonging gastric residence. Indian J. Pharm. Educ. Res. 2004; 38: 172-179.

2. Awasthi R, Pawar V, Kulkarni GT. Floating microparticulate systems: An approach to increase gastric retention. Indian J Pharm. 2010;1(1):17-26.

3. Pawar VK, Kansal S, Garg G, Awasthi R, Singodia D, Kulkarni GT. Gastroretentive dosage forms: a review with special emphasis on floating drug delivery systems. Drug Delivery 2011; 18:97–110.

4. Akala EO. Oral controlled release solid dosage forms. In: Jasti BR, Ghosh TK, eds. Theory and practice of contemporary pharmaceutics. 2nd ed. Florida: CRC Press, 2010; 333–66.

5. Siegel RA, Rathbone MJ. Overview of controlled release mechanisms. In: Siepmann J, ed. undamentals and applications of controlled release drug delivery, advances in delivery science and technology. Controlled Release Society. Netherlands: Springer, 2012; 19–43

6. Chien YW. Novel drug delivery systems. USA: Informa, Healthcare Inc. 2009.

7. Awasthi R, T Kulkarni G. Development of novel gastroretentive floating particulate drug delivery system of gliclazide. Current Drug Delivery. 2012;9(5):437-51.

8. Davis SS. Formulation strategies for absorption window. Drug. Discov. Today. 2005; 10: 249-257.

9. Gnanaprakash K, Shekhar KB, Chetty C. A review on floating drug delivery system of H2 receptors. Research Journal of Pharmacy and Technology. 2011;4(4):502-509.

10. Senthil SP, Sreeja MK, Vincent J, Singh MK. Formulation and In vitro Evaluation of Gastroretentive Floating Tablets of Ivabradine Hydrochloride using Different Polymers. Research Journal of Pharmacy and Technology. 2014;7(9):973-975.

11. Suradkar P, Mishra R, Nandgude T. Overview on Trends in Development of Gastroretentive Drug Delivery System. Research Journal of Pharmacy and Technology. 2019;12(11):5633-5640.

12. Streubel A, Siepmann J, Bodmeier R. Drug delivery to the upper small intestine window using gastroretentive technologies. Curr. Opin. Pharmacol. 2006a: 501-508.

13. Awasthi R, Kulkarni GT. Decades of research in drug targeting to the upper gastrointestinal tract using gastroretention technologies: where do we stand?. Drug Delivery. 2016;23(2):378-94.

14. Bukka R, Patel N, Nargund LV, Prakasam K. Formulation and evaluation of coated floating tablets of captopril. Research Journal of Pharmacy and Technology. 2012;5(7):992-996.

15. Friedman M, Klausner E, Lavy E. Gastroretentive controlled release pharmaceutical dosage forms. US Patent. 2004; 6: 685- 962.

16. Fell JT, Atyabi F, Sharma HL, Mohammad HAH. In vivo evaluation of a novel gastric retentive formulation based on ion exchange resins, Journal of Controlled Release. 1996; 42: 105-113.

17. Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery systems. Expert Opinion on Drug Delivery 2006b; 3: 217-233.

18. Awasthi R, Kulkarni GT. Development and characterization of amoxicillin loaded floating microballoons for the treatment of Helicobacter pylori induced gastric ulcer. Asian Journal of Pharmaceutical Sciences. 2013;8(3):174-80.

19. Gopalakrishnan S, Chenthilnathan A. Formulation and in vitro evaluation of Aceclofenac oral floating tablets. Research Journal of Pharmacy and Technology. 2011;4(4):642-645.

20. Rao GK, Mandapalli PK, Manthri R, Reddy VP. Development and in vivo evaluation of gastroretentive delivery systems for cefuroxime axetil. Saudi Pharmaceutical Journal. 2013;21(1):53-9.

21. Arunkumar N, Rani C, Mohanraj KP. Formulation and in vitro evaluation of oral floating tablets of atorvastatin calcium. Research Journal of Pharmacy and Technology. 2008;1(4):492-495.

22. Nur AO, Zhang JS. Captopril floating and/or bioadhesive tablets: design and release kinetics. Drug Development and Industrial Pharmacy. 2000;26(9):965-969.

Received on 08.02.2020 Modified on 14.04.2020

Research J. Pharm. and Tech. 2021; 14(1):207-213.

DOI: 10.5958/0974-360X.2021.00036.6

Hydration (%)