Devidas Gulabrao Bachhav./ Afr.J.Bio.Sc.

6(9) (2024) 543-555 ISSN: 2663-2187

https://doi.org/ 10.33472/AFJBS.6.9.2024.543-555

Optimizing Gastroretentive Floating Tablets with HPMC and

Sodium Bicarbonate for Controlled Drug Release of Bisoprolol
Devidas Gulabrao Bachhav3*, Kavitha S1, Vanitha C2, Amol Borade4, Touseef Begum5,
Samriti Vohra6, Amit Chandna7, Milind Dilip Phanse8,

1
Department of Biochemistry, School of Allied Health Sciences, the Apollo University Murukambattu
Chittoor Andhra Pradesh 517001.
2
Department of Pharmaceutical Analysis, Seven hills College of Pharmacy, Venkatramapuram,
Tanapalli, Tirupati, Andhra Pradesh 517561.
3
Department of Pharmaceutics, Mahatama Gandhi Vidayamandirs Samajshri Prashantdada Hiray
College of Pharmacy, LVH Marg, Malegaon Camp, Malegaon, Dist-Nashik, Maharastra Pin- 423105.
4
Department of Pharmaceutics, Oriental college of pharmacy, Sanpada, Navi mumbai, Maharashtra,
India. Pin: 400705.
5
Department of Pharmaceutical Sciences, Ibn Sina National College for Medical Studies,
P.O. Box 31906, Jeddah 21418, Kingdom of Saudi Arabia.
6
Department of Pharmacology, Gandhi College of Pharmacy, Karnal, Haryana-132001, India.
7
Department of Pharmaceutics, RP Educational Trust Institute of Pharmacy, Karnal, Haryana-132001,
India.
8
Department of Pharmaceutics, Arvind Gavali College of Pharmacy Jaitapur, Satara, Maharashtra
,India Pin- 415004.
Corresponding Author
Devidas Gulabrao Bachhav3*
3Department of Pharmacutics, Mahatama Gandhi Vidayamandirs Samajshri

Prashantdada Hiray College of Pharmacy, LVH Marg, Malegaon Camp, Malegaon,

Dist-Nashik, Maharastra Pin- 423105.
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Devidas Gulabrao Bachhav./ Afr.J.Bio.Sc. 6(9) (2024) 543-555

ABSTRACT
This study explores the development and evaluation of a floating
Article History gastroretentive drug delivery system (GRDDS) utilizing a
Volume 6,Issue 9, 2024 hydroxypropyl methylcellulose (HPMC) matrix and sodium bicarbonate
Received:21 Mar 2024 as a gas-generating agent to sustain the release of bisoprolol over a
Accepted : 18 Apr 2024
24-hour period. The objective was to formulate a floating tablet that
doi: 10.33472/AFJBS.6.9.2024.543-555
initiates floating within 15 minutes and maintains a consistent drug
release through hydrodynamic balance. The drug release profile was
segmented into various phases: an initial burst in the first hour, followed
by a steady release phase extending up to 8 hours, and concluding with a
tailing off phase up to 12 hours, eventually leading to complete
dissolution by 24 hours. The release kinetics were analysed, assuming
near zero-order kinetics, indicative of a controlled release mechanism.
The influence of polymer concentration on the release rate was
significant, as increased HPMC content slowed the release, providing a
denser gel barrier, while higher levels of sodium bicarbonate enhanced
the buoyancy and modified release dynamics by increasing the surface
area exposed to gastric fluids. This research underscores the potential of
floating GRDDS of bisoprolol in improving the bioavailability and
efficacy of drugs requiring prolonged gastric retention. The study
provides a foundational understanding for optimizing drug release
profiles of bisoprolol in floating tablet formulations.
Keywords: Gastroretentive Drug Delivery System, Floating Tablets,
Controlled Release, Hydroxypropyl Methylcellulose, Sodium
Bicarbonate, Gas-generating agent

INTRODUCTION
Gastroretentive drug delivery systems (GRDDS) represent a significant advancement in the
field of pharmaceutical technology, specifically designed to enhance the delivery of drugs
within the gastrointestinal tract. Among various GRDDS, floating drug delivery systems
(FDDS) are particularly notable. These systems are designed to remain buoyant in the
stomach for an extended period, thereby maximizing the drug’s residence time at the site of
absorption and enhancing bioavailability. This introduction explores the concept, mechanisms,
benefits, and clinical significance of gastroretentive floating drug delivery systems (Namdev
and Jain, 2019, Schneider et al., 2019, Tripathi et al., 2019). The primary goal of FDDS is to
achieve prolonged gastric retention, thus ensuring that the drug remains in the gastric region
for an extended period and is released slowly at the desired rate. This is particularly useful for
drugs that are specifically absorbed from the stomach or the upper part of the small intestine.
Floating drug delivery systems work on the principle of buoyancy. These systems are
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formulated to be less dense than gastric fluids, which allows them to float in the stomach for
an extended period without affecting the gastric emptying rate (Hua, 2020, Jacob et al., 2020,
Das et al., 2021).
The buoyancy of these systems is typically achieved through one of two mechanisms:
gas-forming systems and non-gas forming systems. Gas-forming systems incorporate
ingredients that generate gas upon contact with gastric fluid, thus lowering the density of the
formulation and causing it to float. Non-gas forming systems, on the other hand, are made
from swellable polymers that absorb gastric fluid and swell to a size that prevents their exit
through the pylorus, while remaining light enough to float on the gastric contents. The
importance of gastroretentive systems lies in their ability to improve drug efficacy and patient
compliance (de Souza et al., 2021, Rathor et al., 2021). Many drugs are absorbed more
efficiently in the stomach or upper parts of the intestine. By retaining the drug in the stomach,
FDDS can increase the concentration gradient of the drug between the formulation and the
absorption site, leading to enhanced bioavailability. Floating systems can provide a prolonged
release of the drug, which is beneficial for drugs with a short half-life and those required to act
over a sustained period. This reduces the frequency of dosing and can improve patient
compliance. For drugs that act locally in the stomach, such as antacids or antibiotics for
Helicobacter pylori, FDDS ensures that the drug is released directly at the site of action,
increasing its effectiveness. By providing a more controlled and sustained drug release, FDDS
minimize the fluctuations in plasma drug concentration, thereby maintaining drug levels
within the therapeutic window and reducing side effects. The clinical applications of
gastroretentive floating drug delivery systems are vast and varied. They are particularly useful
for drugs that are soluble only at acidic pH, such as certain antifungal and antibiotic
medications. Additionally, drugs used in the treatment of peptic ulcer disease, such as proton
pump inhibitors and H2 receptor antagonists, benefit greatly from increased retention time in
the stomach (Vrettos et al., 2021, Almutairi et al., 2022, Blynskaya et al., 2022, Grosso and
de-Paz, 2022, Rafiee and Abdul Rasool, 2022).
Moreover, FDDS can be crucial for the treatment of diseases that require a localized action in
the upper part of the small intestine, such as duodenal ulcers. The ability of these systems to
release drugs at a controlled and predictable rate also makes them suitable for chronic
therapies, such as those required for cardiovascular and neurodegenerative diseases, where
consistent drug levels can be crucial for effective management. Despite the benefits, the
development of effective FDDS faces several challenges (Rajora and Nagpal, 2022, Uboldi et
al., 2022). The variability in gastric physiology such as pH and motility, the presence of food,
and differences in the gastric emptying rate can affect the performance of floating systems.
Advances in polymer science, formulation techniques, and a better understanding of gastric
motility are driving the development of more robust and adaptable FDDS. In assumption,
gastroretentive floating drug delivery systems represent a promising approach in the field of
pharmaceutical sciences, offering significant benefits in terms of improving the efficacy and
convenience of drug therapies. As research continues to evolve, these systems are likely to
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become increasingly sophisticated, with the potential to target a wider range of diseases and
conditions more effectively (Rajora and Nagpal, 2022, Uboldi et al., 2022, Mahmoud and
Schulz-Siegmund, 2023, Yoshida and Kojima, 2023).
Bisoprolol is a highly selective β₁-adrenergic receptor blocker commonly prescribed in the
treatment of cardiovascular diseases such as hypertension, angina pectoris, and heart failure.
As a member of the beta-blocker class, bisoprolol works primarily by reducing the heart rate
and cardiac output, which lowers blood pressure and decreases the heart's demand for oxygen.
This pharmacologic profile makes bisoprolol an effective agent in managing long-term
cardiovascular conditions. However, the pharmacokinetics and therapeutic efficacy of
bisoprolol present certain challenges that can be effectively addressed through gastroretentive
drug delivery systems (GRDDS). Bisoprolol has a relatively low oral bioavailability of about
30-40%, primarily due to its partial absorption in the gastrointestinal tract and first-pass
metabolism in the liver. The drug is characterized by a relatively short half-life, typically
around 10-12 hours, necessitating twice-daily dosing to maintain therapeutic plasma
concentrations. Moreover, bisoprolol is predominantly absorbed in the upper gastrointestinal
tract. These properties make maintaining consistent drug levels challenging, impacting patient
compliance and overall therapeutic outcomes (Chaturvedi et al., 2014, Jankovic, 2014,
Hulkower et al., 2015, Kiel and Deedwania, 2015, Ågesen et al., 2019, Aoun and Tabbah,
2019).
The characteristics of bisoprolol make it an ideal candidate for formulation into a
gastroretentive floating drug delivery system for several reasons. By retaining the dosage form
in the stomach and upper gastrointestinal tract, GRDDS can enhance the absorption window
of bisoprolol. This could potentially increase its bioavailability by providing a more prolonged
exposure to its primary absorption sites. Bisoprolol’s absorption in the upper part of the
gastrointestinal tract aligns well with the design of GRDDS, which are engineered to remain
buoyant in gastric fluids. By floating in the stomach, the drug can be released slowly at a
controlled rate, improving the efficiency of drug delivery and reducing the variability in
plasma levels. Incorporating bisoprolol into a floating drug delivery system can extend its
release, allowing for once-daily dosing. This not only improves patient adherence by
simplifying the dosing regimen but also helps maintain more consistent blood levels of the
drug, which is crucial for managing cardiovascular conditions effectively (Digne-Malcolm et
al., 2016, Eguchi, 2016, Wong et al., 2016, Meattini et al., 2017, Sinnott et al., 2017, Tataru
and Barry, 2017). Controlled release of bisoprolol through GRDDS can help mitigate the
peaks and troughs in drug levels associated with conventional dosing, potentially reducing the
risk of side effects commonly linked to higher plasma concentrations, such as bradycardia and
fatigue. Environmental pH changes along the GI tract can affect the solubility and stability of
many drugs. The use of GRDDS ensures that bisoprolol is released in a more controlled
environment, potentially stabilizing its release profile against the variable pH conditions of the
gastrointestinal tract. Given these considerations, the development of a gastroretentive
delivery system for bisoprolol offers a promising approach to enhance its therapeutic efficacy
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and patient compliance. By addressing the limitations associated with the conventional oral
delivery of bisoprolol, GRDDS can significantly improve the management of chronic
cardiovascular diseases, aligning with the goals of modern pharmaceutical care which
emphasize both efficacy and patient-centeredness. This approach underscores the potential of
advanced drug delivery technologies in transforming the treatment landscape for widespread
health conditions (Gach et al., 2017, Tataru and Barry, 2017, Widimský, 2017, Pham et al.,
2018, Aoun and Tabbah, 2019, Kishi and Fujii, 2019, Marti et al., 2024, Maslov et al., 2024).
EXPERIMENTAL
Materials:
Bisoprolol was provided as a complimentary sample by Ranchet Pharma, India. The other
materials used included Hydroxy Propyl Methyl Cellulose K4M obtained from Research Lab
Fine Chemicals in Mumbai, sodium bicarbonate from Loba Chemicals, Carbopol 934P from
S.D. Fine Chemicals in Mumbai, along with talc and magnesium stearate. The equipment
utilized comprised a tablet compression machine from Rotary Tablet Press F.P. Machinery in
Ahmedabad, a UV visible spectrophotometer by Shimadzu Corporation, as well as a
dissolution test apparatus, electronic balance, hardness tester, and friability test apparatus.
Methods:
Manufacturing of Floating Tablets:
Bisoprolol, HPMC (Hydroxy Propyl Methyl Cellulose), Carbopol, and sodium bicarbonate
were each sieved through a number 80 mesh. Subsequently, the drug was blended with these
polymers and additional components according to specified weight ratios. The mixture was
then compressed using a flat-faced punch (5 mm diameter) on an eight-station tableting
machine. The specific formulations are detailed in Table 1 (Shaikh et al., 2011).
Table 1. Formulation table for the gastroretentive formulation
Components Bisoprolol HPMC Carbopol Sodium Magnesium Talc
and Ingredients (mg) K4M 934P bicarbonate stearate
(mg)
GRF1 10 50 10 60 2 1
GRF2 10 70 5 45 2 1
GRF3 10 90 2 30 2 1
GRF4 10 110 1 15 2 1

Evaluation of Floating Tablets:

Hardness Test:
The hardness of the tablets was evaluated using a Pfizer hardness tester, which quantifies the
force needed to crush the tablets, expressed in kilograms per square centimeter (Kg/cm²).
Friability Test:
To assess the friability, we began by removing any loose dust from 10 tablets. These tablets
were then placed in a friabilator and subjected to rotation at 25 revolutions per minute for four
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minutes. After this process, any additional dust was removed, and the weight of the remaining
tablets was recorded. The percentage of friability was calculated using the following formula:

Uniformity of Weight:
Each of the 20 tablets was carefully cleaned and subsequently weighed using an electronic
balance to verify uniform weight throughout the batch.
In Vitro Floating Studies:
The floating time of the tablets was observed using a USP dissolution apparatus-II, which was
set to stir at 50 rpm in 900 ml of 0.1N HCl. The solution was maintained at a temperature of
37±0.5°C. This test measured the duration for which the tablets remained buoyant, including
any initial delay before the tablets started to float. The observation was made visually.
Swelling Index:
Tablets were accurately weighed and immersed in 50 ml of water. After remaining in the water
for 60 minutes, they were removed and carefully dried using filter paper to remove any
surface moisture, then weighed again. The swelling index was determined using the following
formula:

In Vitro Dissolution Studies:

Dissolution testing of the floating tablets was conducted using a USP paddle apparatus, set to
operate at 50 rpm in 900ml of 0.1N HCl, while maintaining a constant temperature of
37±0.5°C. Periodically, 5ml samples were withdrawn from the dissolution medium and
immediately replaced with fresh medium to maintain a consistent volume. The rate of drug
release was analyzed by measuring the absorbance at 238 nm using a UV-Visible
spectrophotometer.
Data Analysis Models:
The drug release data from the studies were analyzed using various kinetic models to
understand the release mechanics and efficiency of the floating tablet formulations. These
models included:
Zero-order kinetic model, which plots cumulative percent of drug released versus time,
indicating a constant release rate.
First-order kinetic model, which uses the log of the percent drug remaining versus time to
show a release rate dependent on the drug concentration.
Higuchi's model, which correlates cumulative percent drug released with the square root of
time, suggesting a diffusion-based release.
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Korsmeyer-Peppas equation, which plots the log of the cumulative percent drug released
versus log time, useful for understanding the mechanism of drug release when the release
behavior does not follow conventional patterns.
Each model provides distinct insights into the release characteristics of the floating tablet
formulations.
RESULTS
In this study, we developed hydrodynamically balanced systems (HBS) of Bisoprolol using
hydroxypropyl methylcellulose (HPMC) and sodium bicarbonate as a gas-generating agent in
various ratios, aiming to achieve controlled drug release through floating tablets. The
evaluation of these HBS tablets focused on several critical quality metrics:
Hardness: The tablets exhibited a consistent hardness, with values ranging from 4.28 to 5.21
Kg/cm².
Friability: The tablets demonstrated excellent durability, with friability percentages between
0.81% and 0.88%.
Weight Uniformity: All batches-maintained uniformity within acceptable limits, reflecting
consistent manufacturing quality.
Swelling Index: The swelling index increased with higher concentrations of polymer and
sodium bicarbonate, indicating effective tablet expansion under gastric conditions.
The floating characteristics of the tablets were also visually assessed:
Floating Lag Time: Varied from 4.3 to 8.9 minutes, indicating the time taken for the tablets to
start floating.
Floating Time: The tablets-maintained buoyancy for durations ranging from 19 to 22 hours,
ensuring prolonged gastric retention.
The composition of the tablets influenced the drug release dynamics:
Drug Release: Increased polymer content resulted in a slower release rate over 10 hours,
whereas higher sodium bicarbonate levels accelerated the release.
To elucidate the release mechanism, we applied various kinetic models:
Drug Release Kinetics: Linear regression analysis supported first-order release kinetics, with
R² values ranging from 0.8364 to 0.9965, indicative of a consistent drug release rate. The
release patterns also conformed to the Korsmeyer-Peppas model, suggesting a predominantly
diffusion-based release mechanism.
Table 2. Evaluation of the formulations
Code of formulations GRF1 GRF2 GRF3 GRF4
Hardness (Kg/cm ) 2 4.28 4.77 5.21 4.87
Friability (% w/w) 0.82 0.81 0.88 0.87
Average weight (mg) 130.4 130.3 129.7 133.2
Floating lag time (min) 8.9 6.7 4.3 5.7
Floating time (hrs) 19 20 22 21
Swelling index (%) 170.34 156.7 140.5 139.5
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150

GRF1

% Drug Release
100
GRF2
GRF3
50 GRF4

0
0 10 20 30
Time (Hr)

Figure 1. In vitro drug release study

Table 3. Pharmacokinetic and mathematical modelling of the in vitro release profile
Code of Zero First Higuchi Peppas Hixson
formulations order order Crowell
2
GRF1 R 0.926 0.9819 0.8364 0.9945 0.9698
Slope 0.2874 -0.0019 9.0904 2.0663 0.0022
Intercept -38.36 1.5556 -101.23 -4.0456 0.6383
2
GRF2 R 0.9285 0.9861 0.8396 0.995 0.9628
Slope 0.2797 -0.0019 8.8526 2.0922 0.0021
Intercept -37.303 1.7332 -98.586 -4.1241 0.628
2
GRF3 R 0.9291 0.9866 0.8404 0.9961 0.9596
Slope 0.2677 -0.0019 8.4794 2.129 0.0021
Intercept -35.781 1.552 -94.498 -4.238 0.6009
2
GRF4 R 0.9306 0.9863 0.8467 0.9965 0.9955
Slope 0.2671 -0.002 9.4894 2.3071 0.003
Intercept -35.803 1.602 -93.499 -4.238 0.6009

DISCUSSION
The evaluation of hydrodynamically balanced floating tablet formulations (GRF1 to GRF4)
indicates distinct characteristics and performance across the different formulations, as detailed
in the provided data. Discussion centers on the hardness, friability, average weight, floating
characteristics, swelling index, and the kinetic models applied to understand the drug release
mechanisms.The hardness of the tablets varied slightly across the formulations, with GRF3
exhibiting the highest hardness (5.21 Kg/cm²), suggesting a more robust tablet structure. This
correlates with its marginally higher friability (0.88%), although all formulations remained
below 1% friability, indicating excellent tablet integrity. The variation in hardness may be
attributed to differences in compression force during manufacturing or the ratio of ingredients,
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affecting the compactness and mechanical strength of the tablets. The average weight of the
tablets showed minor discrepancies, all within an acceptable range for uniform dosage. The
highest weight was observed in GRF4 (133.2 mg), which could influence both drug release
and floating behavior. The swelling index, which indicates the tablet's ability to absorb water
and expand, was highest in GRF1 (170.34%) and decreased progressively through the series.
This reduction might be due to varying polymer concentrations, affecting the gel-forming
ability and, consequently, the tablet’s buoyancy and drug release. Floating lag time decreased
from GRF1 to GRF3, improving the promptness of buoyancy, which is crucial for maintaining
the tablet in the gastric region. This quicker onset of floating could be due to modifications in
the formulation, such as the balance between hydrocolloid and gas-forming agents. The
floating time was excellent across all formulations, with tablets maintaining buoyancy for 19
to 22 hours, ensuring prolonged gastric retention for sustained drug release. The kinetic
analysis shows a strong correlation in the first-order model across all formulations (R² > 0.98),
indicating that the drug release rate is concentration dependent. This model was confirmed as
the most fitting, supported by high R² values in the Peppas model as well, which further
suggests that the drug release mechanism is predominantly diffusion-controlled, particularly
for GRF3 and GRF4, where the Peppas R² values were highest. The consistent slopes and
intercepts across the kinetic models further reinforce the uniform behavior of these
formulations under test conditions.
CONCLUSION
The formulation variations, as represented by GRF1 through GRF4, demonstrate the impact of
minor compositional changes on the physical and release characteristics of floating tablets.
The data suggest a careful balance between polymer content for swelling, hardness for
mechanical strength, and the correct proportion of gas-forming agents to optimize both
immediate and sustained release properties in a gastric setting. The kinetic analysis not only
assists in confirming the release dynamics but also aligns with the practical outcomes seen in
floating lag and duration, corroborating the formulation strategy’s effectiveness for sustained
drug delivery via floating tablets. Determining the "best" formulation among GRF1, GRF2,
GRF3, and GRF4 depends on specific criteria related to the intended therapeutic use and
desired characteristics of the floating tablets. GRF3 has the highest hardness (5.21 Kg/cm²),
which suggests it may be the most robust and potentially the most resistant to physical stress
during handling and administration. All formulations demonstrate excellent friability (all
below 1%), indicating good durability. GRF2 and GRF1 have slightly lower friability (0.81%
and 0.82% respectively), which might be marginally preferable. Weight consistency is crucial
for dose accuracy. All formulations are relatively consistent, with GRF2 and GRF3 showing
the least deviation in average weight. GRF1 exhibits the highest swelling index (170.34%),
which could indicate better performance in gastric fluid, potentially enhancing gastric
retention. Floating Lag Time: GRF3 begins to float the quickest (4.3 minutes). GRF3 also
maintains buoyancy the longest (22 hours), which is beneficial for sustained drug release and
prolonged gastric retention. The Peppas model, which describes the drug release mechanism,
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shows the highest R² value for GRF4 (0.9965), suggesting a highly predictable
diffusion-based release mechanism. However, GRF3 is also strong in this area (R² = 0.9961).
GRF3 appears to be the optimal formulation overall, balancing quick onset of floating,
prolonged floating time, robust hardness, consistent weight, and strong performance in drug
release kinetics. This formulation would likely provide the most reliable and sustained drug
delivery in a gastric environment. However, the choice of the best formulation can also
depend on additional factors not covered in the data, such as the cost of ingredients, ease of
manufacturing, patient compliance, and specific clinical outcomes related to the drug being
delivered.
REFERENCE
ÅGESEN, F. N., WEEKE, P. E., TFELT-HANSEN, P. & TFELT-HANSEN, J. 2019.
Pharmacokinetic variability of beta-adrenergic blocking agents used in cardiology.
Pharmacol Res Perspect, 7, e00496.
ALMUTAIRI, M., SRINIVASAN, P., ZHANG, P., AUSTIN, F., BUTREDDY, A., ALHARBI,
M., BANDARI, S., ASHOUR, E. A. & REPKA, M. A. 2022. Hot-Melt extrusion
coupled with pressurized carbon dioxide for enhanced processability of pharmaceutical
polymers and drug delivery applications - An integrated review. Int J Pharm, 629,
122291.
AOUN, M. & TABBAH, R. 2019. Beta-blockers use from the general to the hemodialysis
population. Nephrol Ther, 15, 71-76.
BLYNSKAYA, E. V., TISHKOV, S. V., VINOGRADOV, V. P., ALEKSEEV, K. V.,
MARAKHOVA, A. I. & VETCHER, A. A. 2022. Polymeric Excipients in the
Technology of Floating Drug Delivery Systems. Pharmaceutics, 14.
CHATURVEDI, S., LIPSZYC, D. H., LICHT, C., CRAIG, J. C. & PAREKH, R. 2014.
Pharmacological interventions for hypertension in children. Evid Based Child Health,
9, 498-580.
DAS, S., KAUR, S. & RAI, V. K. 2021. Gastro-retentive drug delivery systems: a recent
update on clinical pertinence and drug delivery. Drug Deliv Transl Res, 11, 1849-1877.
DE SOUZA, M. P. C., DE CAMARGO, B. A. F., SPÓSITO, L., FORTUNATO, G. C.,
CARVALHO, G. C., MARENA, G. D., MENEGUIN, A. B., BAUAB, T. M. &
CHORILLI, M. 2021. Highlighting the use of micro and nanoparticles based-drug
delivery systems for the treatment of Helicobacter pylori infections. Crit Rev
Microbiol, 47, 435-460.
DIGNE-MALCOLM, H., FRISE, M. C. & DORRINGTON, K. L. 2016. How Do
Antihypertensive Drugs Work? Insights from Studies of the Renal Regulation of
Arterial Blood Pressure. Front Physiol, 7, 320.
EGUCHI, K. 2016. New Insight into Effects of β-Blockers on Arterial Functions. Pulse
(Basel), 3, 190-4.
 Page 553 of 13

Devidas Gulabrao Bachhav./ Afr.J.Bio.Sc. 6(9) (2024) 543-555

GACH, O., FALQUE, B., CANIVET, A., KRZESINSKI, F., KRZESINSKI, J. M. &
LANCELLOTTI, P. 2017. [Bipressil® : first single-pill combination of bisoprolol and
perindopril arginine]. Rev Med Liege, 72, 260-265.
GROSSO, R. & DE-PAZ, M. V. 2022. Scope and Limitations of Current Antibiotic Therapies
against Helicobacter pylori: Reviewing Amoxicillin Gastroretentive Formulations.
Pharmaceutics, 14.
HUA, S. 2020. Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal
Tract - Influence of Physiological, Pathophysiological and Pharmaceutical Factors.
Front Pharmacol, 11, 524.
HULKOWER, S., AIKEN, B. A. & STIGLEMAN, S. 2015. Clinical inquiry: what is the best
beta-blocker for systolic heart failure? J Fam Pract, 64, 122-3.
JACOB, S., NAIR, A. B., PATEL, V. & SHAH, J. 2020. 3D Printing Technologies: Recent
Development and Emerging Applications in Various Drug Delivery Systems. AAPS
PharmSciTech, 21, 220.
JANKOVIC, S. M. 2014. Pharmacokinetics of selective β1-adrenergic blocking agents:
prescribing implications. Expert Opin Drug Metab Toxicol, 10, 1221-9.
KIEL, R. G. & DEEDWANIA, P. 2015. The safety and tolerability of beta blockers in heart
failure with reduced ejection fraction: is the current underutilization of this
evidence-based therapy justified? Expert Opin Drug Saf, 14, 1855-63.
KISHI, T. & FUJII, E. 2019. Carvedilol and bisoprolol as initial therapy for adult hypertension
without compelling indications. Hypertens Res, 42, 496-503.
MAHMOUD, D. B. & SCHULZ-SIEGMUND, M. 2023. Utilizing 4D Printing to Design
Smart Gastroretentive, Esophageal, and Intravesical Drug Delivery Systems. Adv
Healthc Mater, 12, e2202631.
MARTI, H. P., PAVÍA LÓPEZ, A. A. & SCHWARTZMANN, P. 2024. Safety and tolerability
of β-blockers: importance of cardioselectivity. Curr Med Res Opin, 40, 55-62.
MASLOV, L. N., NARYZHNAYA, N. V., VORONKOV, N. S., KURBATOV, B. K.,
DERKACHEV, I. A., RYABOV, V. V., VYSHLOV, E. V., KOLPAKOV, V. V.,
TOMILOVA, E. A., SAPOZHENKOVA, E. V., SINGH, N., FU, F. & PEI, J. 2024. The
role of β-adrenergic receptors in the regulation of cardiac tolerance to
ischemia/reperfusion. Why do β-adrenergic receptor agonists and antagonists protect
the heart? Fundam Clin Pharmacol.
MEATTINI, I., CURIGLIANO, G., TERZIANI, F., BECHERINI, C., AIROLDI, M.,
ALLEGRINI, G., AMOROSO, D., BARNI, S., BENGALA, C., GUARNERI, V.,
MARCHETTI, P., MARTELLA, F., PIOVANO, P., VANNINI, A., DESIDERI, I.,
TARQUINI, R., GALANTI, G., BARLETTA, G. & LIVI, L. 2017. SAFE trial: an
ongoing randomized clinical study to assess the role of cardiotoxicity prevention in
breast cancer patients treated with anthracyclines with or without trastuzumab. Med
Oncol, 34, 75.
 Page 554 of 13

Devidas Gulabrao Bachhav./ Afr.J.Bio.Sc. 6(9) (2024) 543-555

NAMDEV, A. & JAIN, D. 2019. Floating Drug Delivery Systems: An Emerging Trend for the
Treatment of Peptic Ulcer. Curr Drug Deliv, 16, 874-886.
PHAM, D., ADDISON, D., KAYANI, W., MISRA, A., JNEID, H., RESAR, J., LAKKIS, N.
& ALAM, M. 2018. Outcomes of beta blocker use in cocaine-associated chest pain: a
meta-analysis. Emerg Med J, 35, 559-563.
RAFIEE, M. H. & ABDUL RASOOL, B. K. 2022. An Overview of Microparticulate Drug
Delivery System and its Extensive Therapeutic Applications in Diabetes. Adv Pharm
Bull, 12, 730-746.
RAJORA, A. & NAGPAL, K. 2022. A Critical Review on Floating Tablets as a Tool for
Achieving Better Gastric Retention. Crit Rev Ther Drug Carrier Syst, 39, 65-103.
RATHOR, S., AAMIR, S., BHATT, D. C., KUMAR, K. & KUMAR, V. 2021. A
Comprehensive Review on Microbubble Concept, Development and Its Application in
Therapeutic Drug Delivery and Clinical Management of Disease. Curr Pharm
Biotechnol, 22, 1424-1443.
SCHNEIDER, F., KOZIOLEK, M. & WEITSCHIES, W. 2019. In Vitro and In Vivo Test
Methods for the Evaluation of Gastroretentive Dosage Forms. Pharmaceutics, 11.
SHAIKH, K. N., PAYGHAN, S. A. & DESOUZA, J. I. 2011. Formulation of gastroretentive
drug delivery system (floating tablets) of nifedipine. International Journal of
Pharmaceutical Sciences and Research, 2, 2929.
SINNOTT, S. J., TOMLINSON, L. A., ROOT, A. A., MATHUR, R., MANSFIELD, K. E.,
SMEETH, L. & DOUGLAS, I. J. 2017. Comparative effectiveness of fourth-line
anti-hypertensive agents in resistant hypertension: A systematic review and
meta-analysis. Eur J Prev Cardiol, 24, 228-238.
TATARU, A. P. & BARRY, A. R. 2017. A Systematic Review of Add-on Pharmacologic
Therapy in the Treatment of Resistant Hypertension. Am J Cardiovasc Drugs, 17,
311-318.
TRIPATHI, J., THAPA, P., MAHARJAN, R. & JEONG, S. H. 2019. Current State and Future
Perspectives on Gastroretentive Drug Delivery Systems. Pharmaceutics, 11.
UBOLDI, M., MELOCCHI, A., MOUTAHARRIK, S., PALUGAN, L., CEREA, M.,
FOPPOLI, A., MARONI, A., GAZZANIGA, A. & ZEMA, L. 2022. Administration
strategies and smart devices for drug release in specific sites of the upper GI tract. J
Control Release, 348, 537-552.
VRETTOS, N. N., ROBERTS, C. J. & ZHU, Z. 2021. Gastroretentive Technologies in
Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug
Bioavailability and Patient Compliance Implications. Pharmaceutics, 13.
WIDIMSKÝ, J. 2017. [COSYREL - an efficient fixed combination for treatment of
hypertension, stable ISHD and heart failure]. Vnitr Lek, 63, 667-671.
WONG, G. W., BOYDA, H. N. & WRIGHT, J. M. 2016. Blood pressure lowering efficacy of
beta-1 selective beta blockers for primary hypertension. Cochrane Database Syst Rev,
3, Cd007451.
 Page 555 of 13

Devidas Gulabrao Bachhav./ Afr.J.Bio.Sc. 6(9) (2024) 543-555

YOSHIDA, T. & KOJIMA, H. 2023. Oral Drug Delivery Systems Applied to Launched
Products: Value for the Patients and Industrial Considerations. Mol Pharm, 20,
5312-5331.