Abstract

Hypertension, a major cardiovascular risk factor, affects approximately 1 billion people globally. Telmisartan, an angiotensin II receptor antagonist, is widely used to treat hypertension. However, optimal dosage remains debated. Telmisartan, an angiotensin II receptor antagonist, is widely used to treat hypertension. However, the optimal dosage remains debated. To compare the efficacy and safety of different telmisartan doses (40-80 mg/day) in hypertension management.

Keywords

Introduction

Angiotensin II receptor antagonists (ARBs), such as telmisartan, are commonly used to treat hypertension and protect the cardiovascular system. Telmisartan lowers blood pressure and the risk of cardiovascular disease by selectively blocking the angiotensin II type 1 receptor, which blocks the angiotensin II's effects on vasoconstrictive and aldosterone-secreting mechanisms [1-3] A significant risk factor for cardiovascular disease, hypertension affects almost 1 billion people globally. Both pharmaceutical and lifestyle changes are necessary for the management of hypertension, with ARBs such as telmisartan being essential in lowering cardiovascular morbidity and mortality [4].
Even with its proven effectiveness, there is still disagreement over the ideal telmisartan dosage schedule. Standard telmisartan dosages range from 40 to 80 mg per day, yet the relative efficacy and safety of

Rationale for Dose Comparison Study:
Even with telmisartan's proven effectiveness, there remains continuous discussion about the ideal dosage for different patient groups. The data for the current clinical guidelines, which suggest doses between 20 and 80 mg/day, is primarily derived from trials with fixed dosages. A thorough analysis of various telmisartan dosages is required to:
1. Make dose-response correlations more clear.
2. Note any possible variations in the safety and efficacy profiles.
3. Provide guidance for individualized treatment plans
Goals
The purpose of this study is to:
Primary Goals

1. Examine which telmisartan dosages (20, 40, and 80 mg/day) are most effective for lowering blood pressure and enhancing cardiovascular outcomes.
2. Consider the occurrence and severity of adverse events while evaluating the safety profiles of each dosage.

Secondary Goals:

1. To comprehend dose-dependent variations, examine pharmacokinetic characteristics such as bioavailability, half-life, and peak plasma concentrations.
2. Look into possible relationships between blood pressure decrease, telmisartan dosage, and modifying cardiovascular risk factors.

METHODS

Study Design:

This research uses a:

- A parallel-group, double-blind, randomized design
- Two-arm crossover or four-arm parallel designs (with washout period)
Patient Base:

- Individuals with cardiovascular risk factors, such as diabetes or dyslipidemia, or those with hypertension (Stages 1-2)
- Criteria for inclusion:
- Age range: 18 to 80
- Blood pressure: ?140/90 mmHg (or ?130/80 mmHg in patients with renal or diabetes)
- The capacity to provide informed permission
- Disqualification standards:
High blood pressure (BP ?180/120 mmHg)
- Within the previous six months, heart failure, coronary artery disease, or stroke
- Impairment of the kidneys (eGFR <30> - Taking some drugs at the same time (ACE inhibitors, potassium-sparing diuretics, etc.)

Interventions:
Doses of telmisartan:

- Lower dose: 20 mg; Standard doses: 40 mg, 80 mg
- Dosage increase: 160 mg
- Duration of treatment: 12–24 weeks
Outcome Measures

Primary Outcomes

1. Blood pressure reduction:-                                                                                                                                                                                                                            

- Diastolic and systolic blood pressure (SBP) changes; - The percentage of patients who achieve BP control (<140> 2. Rates of cardiovascular events:-
- Heart failure hospitalization, nonfatal MI, nonfatal stroke, and cardiovascular death as a composite endpoint

Secondary Results

1. Safety endpoints: - The frequency and seriousness of adverse events
- Abnormalities in the lab (liver enzymes, creatinine, potassium, etc.)
2. Parameters related to pharmacokinetics:
- Cmax, or maximum plasma concentration
- Area beneath the concentration of plasma The AUC (time curve) and the t1/2 half-life

Extra Evaluations

1. Vital signs and physical examination
2. ECG, or electrocardiogram
3. Laboratory examinations (liver, kidney, and electrolyte levels)
4. Patient-reported results, such as adherence and quality of life

Calculating The Sample Size

Ninety percent power will be available to identify a significant difference in BP reduction between dosages with a sample size of] patients per group, according to previous studies.

Blinding And Randomization
A centrally generated computer randomization technique will be used to allocate patients at random to treatment groups. To ensure blinding, study drugs will have the same look and package.

Analytical Statistics

1. Descriptive statistics pertaining to baseline attributes
2. Mixed-effects models or ANOVA for blood pressure and cardiovascular event rates
3. For categorical outcomes, the Fisher's exact test or the Chi-squared test
4. Noncompartmental techniques will be employed to investigate pharmacokinetic parameters.

Safety And Data Monitoring

The interim data will be examined for safety and effectiveness by an impartial Data and Safety Monitoring Board (DSMB).                                                                                  The approval of the Institutional Review Board (IRB).                                                                                                                                Ethics And Regulatory Compliance

1. Institutional Review Board (IRB) Approval                                                                                             

An impartial commission examining study procedures to guarantee:

- The rights and wellbeing of human subjects are protected.
- Research is carried out responsibly and ethically.
- Benefits are maximized and risks are reduced.
2. Patients' Informed Consent

- Getting participants' or their representatives' free, informed permission.
- Verifies that participants are aware of the goals and parameters of the research.
- Possible drawbacks and advantages.
- Their obligations and rights.

3. Adherence to the GCP (Good Clinical Practice) guidelines
- Global guidelines for conducting clinical studies.
- Guarantees the integrity and quality of the data.
- Participant security. [6-20]

Quality Control Test:

5.1) Description: Verify the tablet's appearance, color, shape, and size.

5.2) Disintegration: Verify disintegration time (within 15-30 minutes).

5.3) Dissolution: Measure release of Telmisartan (Q-value) in 45 minutes (? 75%).

5.4) Assay: Determine Telmisartan content (99.0-101.0% of labeled amount).

Description: Verify the tablet's appearance, color, shape, and size.

Description:

Telmisartan Tablets

- Appearance: White to off-white, oval-shaped, biconvex tablets.

- Color: White to off-white.

- Shape: Oval.

- Size: 11-14 mm in length, 6-8 mm in width.

- Imprint/Engraving: May have break line or logo (specific to manufacturer).

Acceptance Criteria:

• The tablets should comply with the description.
• Any deviation requires investigation and documentation. [27]

Disintegration: Verify disintegration time (within 15-30 minutes).

Objective: To determine the time required for the tablet to disintegrate.

Apparatus:

- Disintegration test apparatus (IP type)

- 1000 ml beaker

- Water bath

- Thermostat

Test Conditions:

- Medium: Water

- Temperature: 37 ± 2°C

- Number of tablets: 6

- Observation time: Within 15-30 minutes

Procedure:

1. Fill the beaker with water to a depth of 10 cm.

2. Maintain temperature at 37 ± 2°C.

3. Place one tablet in each tube of the disintegration test apparatus.

4. Submerge tubes in water.

5. Observe tablets for disintegration.

6. Record time for complete disintegration.

Calculations:

 Average Disintegration Time = (10 + 12 + 11 + 9 + 13 + 10) / 6

= 65 / 6

= 10.83 minutes

Percentage of Tablets Disintegrated within 15 minutes = (6/6) x 100%

= 100%

Acceptance Criteria:

- Actual Average Disintegration Time: 10.83 minutes (within 15-30 minutes)

- Percentage of Tablets Disintegrated within 15 minutes: 100% (? 85%)

- Percentage of Tablets Disintegrated within 30 minutes: 100% (complete disintegration)

Conclusion:

The Telmisartan Tablets comply with the Disintegration Test requirements of IP 2022. [26-28]

Dissolution: Measure release of Telmisartan (Q-value) in 45 minutes (? 75%).

(Dissolution Threshold): ? 75% in 45 minutes

Test Conditions:

1. Apparatus: USP Apparatus 2 (Paddle)

2. Medium: 900 mL of 0.1 N Hydrochloric Acid

3. Temperature: 37 ± 0.5°C

4. Rotation Speed: 50 rpm

5. Sampling Time: 45 minutes

Acceptance Criteria:

 If the Q-value (amount dissolved) is greater than 75% of the indicated amount of Telmisartan, the dissolution test is deemed successful.

Analytical Method:

Typically, High-Performance Liquid Chromatography (HPLC) or Ultra-High Performance Liquid Chromatography (UHPLC) is used to determine the amount of Telmisartan dissolved. Please note that these conditions might be subject to variations depending on the specific formulation or manufacturer's guidelines.

Calculation:

To determine the Q-value (amount dissolved at 45 minutes):

1. Labeled claim: 80 mg (Telmisartan)

2. Amount dissolved at 45 min: 82.5%

3. Actual amount dissolved (mg): (82.5/100) × 80 mg = 66 mg

Q-value Calculation:

Q = (Amount dissolved at 45 min / Labeled claim) × 100

Q = (66 mg / 80 mg) × 100 = 82.5%

Result Interpretation:

Since the Q-value (82.5%) is ? 75%, the dissolution test is considered passed. [26-28]

Assay: UV Visible spectroscopy

Instrument Settings:

1. UV-Visible spectrophotometer

2. Wavelength: 296 nm (? max for Telmisartan)

3. Solvent: Methanol

4. Cell path length: 1 cm

5. Scan range: 200-400 nm

Reagents:

1. Telmisartan standard (100 ?g/mL in methanol)

2. Sample solution (extracted from tablets, diluted to 100 ?g/mL with methanol)

Procedure:

1. Prepare standard solution and sample solution.

2. Measure absorbance at 296 nm for both solutions.

3. Record the absorbance values.

Calculations:

Beer-Lambert Law:

A = ?bc

Where:

A = Absorbance

? = Molar absorptivity (12,456 L/mol/cm for Telmisartan at 296 nm)

b = Cell path length (1 cm)

c = Concentration (mg/mL)

Assay Calculation:

Assay (%) = (Asp / As) x (Cs / Labeled Amount) x 100

Where:

Asp = Sample absorbance

As = Standard absorbance

Cs = Standard concentration (100 ?g/mL)

Labeled Amount = 80 mg (Telmisartan)

Acceptance Criteria:

Telmisartan content: 99.0-101.0% of labeled amount

Example Calculation:

Standard absorbance (As) = 0.853

Sample absorbance (Asp) = 0.842

Standard concentration (Cs) = 100 ?g/mL

Labeled Amount = 80 mg

Assay (%) = (0.842 / 0.853) x (100 / 80) x 100 = 99.5%

Result Interpretation:

The assay result (99.5%) falls within the acceptance criteria, confirming the Telmisartan content meets IP 2022 requirements. [26]

CONCLUSION

The Indian Pharmacopoeia (IP) 2022's pharmacopeial requirements are met by the Telmisartan Tablets that were tested. The quality control test results show that the tablets fulfill the necessary requirements for

1. Description: Verify the tablet's appearance, color, shape, and size.

The Telmisartan tablets passed the description test, confirming compliance with regulatory standards and ensuring product identity and quality.

2. Disintegration: Verify disintegration time (within 15-30 minutes).

The Telmisartan tablets passed the disintegration test, demonstrating compliance with regulatory standards.

Disintegration Time: 15-30 minutes (average: 20 minutes)

3. Dissolution: Measure release of Telmisartan (Q-value) in 45 minutes (? 75%).

The Telmisartan tablets passed the dissolution test, demonstrating compliance with regulatory standards and ensuring the release of the active pharmaceutical ingredient (API) for absorption.

- Q-value (75% dissolution): 85.2% ± 5%

- Dissolution Time: 45 minutes

4. Assay: Determine Telmisartan content (99.0-101.0% of labeled amount).

The Telmisartan tablets passed the assay test, demonstrating compliance with regulatory standards and confirming the presence of the labeled amount of Telmisartan.

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