Comprehensive Overview of ICATIBANT ACETATE (CAS No. 130308-48-4) Manufactured by Swapnroop Drugs & Pharmaceuticals

Q1: What is ICATIBANT ACETATE manufactured by Swapnroop Drugs & Pharmaceuticals? 🧪💉

Icatibant Acetate is a synthetic decapeptide and a selective bradykinin B2 receptor antagonist. It is primarily used in the treatment of Hereditary Angioedema (HAE) — a rare genetic disorder that leads to sudden and severe swelling of the skin and mucous membranes.

👨‍🔬 Swapnroop Drugs & Pharmaceuticals manufactures Icatibant Acetate as an Active Pharmaceutical Ingredient (API) under strict cGMP guidelines, ensuring purity, safety, and therapeutic efficacy.

🔬 Chemical Identity:

Chemical Name: Icatibant Acetate
CAS Number: 30308-48-4
Molecular Formula: C₅₉H₉₀N₁₈O₁₄ (free base)
Molecular Weight: ~1304.5 g/mol (free base)
Structure: Synthetic peptide composed of 10 amino acid residues

💡 Key Characteristics:

Peptide nature: Designed to mimic bradykinin but blocks its action
Acetate form: Increases solubility and improves formulation stability
Water-soluble: Facilitates parenteral (injection) delivery
Manufactured under sterile and peptide-specific facilities at Swapnroop

🧬 Mechanism of Action:

Bradykinin is a natural molecule that causes inflammation, pain, and swelling during HAE attacks.
Icatibant Acetate blocks the bradykinin B2 receptor, preventing these effects.
Rapidly reverses swelling in HAE patients within hours of administration.

🏭 Manufacturing at Swapnroop:

Swapnroop Drugs & Pharmaceuticals ensures:

High purity peptide synthesis
cGMP-compliant production
Rigorous quality control testing
Regulatory documentation such as CoA, MSDS, and stability data

📦 API Applications:

Icatibant Acetate API is supplied to:

Pharmaceutical formulation companies for injectable drug production
Export markets with appropriate regulatory certifications (e.g., WHO-GMP, EU-GMP)

🌐 Clinical Use:

Indication: Treatment of acute attacks of Hereditary Angioedema (HAE) in adults
Brand Example: Firazyr® (Reference listed drug)
Route of Administration: Subcutaneous injection

🧾 Summary Table:

Parameter	Details
API Name	Icatibant Acetate
CAS Number	30308-48-4
Therapeutic Class	Bradykinin B2 receptor antagonist
Indication	Hereditary Angioedema (HAE)
Manufacturer	Swapnroop Drugs & Pharmaceuticals
Dosage Form (use)	Injectable solution
Route of Admin	Subcutaneous

Q2: What is ICATIBANT ACETATE by Swapnroop Drugs and Pharmaceuticals used for? 💉🩺

Icatibant Acetate manufactured by Swapnroop Drugs & Pharmaceuticals is used as an Active Pharmaceutical Ingredient (API) in the treatment of:

🧬 Hereditary Angioedema (HAE):

A rare genetic disorder caused by C1-esterase inhibitor deficiency.
Results in excess bradykinin, leading to episodic swelling (angioedema) in various parts of the body — including the face, limbs, airway, and digestive tract.

🚑 Primary Use of Icatibant Acetate:

💊 Therapeutic Use	Details
Indication	Treatment of acute HAE attacks
Mechanism	Blocks bradykinin B2 receptors, stopping swelling and inflammation
Effect	Rapid relief of pain, swelling, and discomfort during attacks
Onset	Clinical response typically begins within 30 minutes to 2 hours

🧫 Notable Clinical Benefits:

Avoids need for corticosteroids or epinephrine in HAE attacks
Particularly beneficial when airway swelling (laryngeal edema) is present — a medical emergency
Self-injectable in many formulations (as in branded “Firazyr®”)

🌍 Target Patients:

Adults diagnosed with Hereditary Angioedema type I or II
Patients with recurrent, unpredictable, and severe swelling episodes

✅ Summary:

Icatibant Acetate is a life-saving peptide-based therapeutic used during acute HAE attacks. It works by directly blocking bradykinin, the mediator responsible for life-threatening swelling.

Q3: What are the physicochemical properties of ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals? ⚗️📐

Here are the key physicochemical properties of Icatibant Acetate API:

🔬 Basic Information:

Property	Value
Chemical Name	Icatibant Acetate
CAS Number	30308-48-4
Molecular Formula	C₅₉H₉₀N₁₈O₁₄ (free base)
Molecular Weight	~1304.5 g/mol (free base)
Chemical Class	Synthetic Decapeptide
Physical Appearance	White to off-white lyophilized powder or solid
Solubility	Freely soluble in water and aqueous buffers
pKa	Multiple (due to peptide functional groups)
Melting Point	Not sharply defined (peptides tend to decompose)
Hygroscopicity	Slightly hygroscopic (requires desiccant in storage)
Optical Activity	Levorotatory (specific rotation varies by batch)
Peptide Sequence	D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg

🧬 Other Properties:

Isoelectric Point (pI): ~5.5–6.5 (estimated from amino acid composition)
Stability: Stable under dry, cool conditions in sealed containers; sensitive to moisture, light, and oxidizing agents
Solvent Compatibility: Compatible with aqueous buffers, saline, and select polar solvents

⚠️ Important Notes:

As a peptide drug, Icatibant Acetate is sensitive to heat and enzymatic degradation.
It must be stored at controlled temperatures (typically 2–8°C for formulations, or room temp for the API if sealed and dry).

Q4: How is ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals synthesized? 🧪🧬

Icatibant Acetate is synthesized via solid-phase peptide synthesis (SPPS) — a method widely used for making therapeutic peptides with high purity and specificity. Swapnroop Drugs & Pharmaceuticals applies GMP-compliant techniques and automated synthesizers to ensure consistency and regulatory acceptance.

🔄 Synthesis Process Overview:

🧱 1. Solid-Phase Peptide Synthesis (SPPS):

Starting Material: A resin-bound protected amino acid (typically Rink amide or Wang resin).
Sequential Coupling:
- Amino acids are added one at a time using Fmoc (9-fluorenylmethyloxycarbonyl) or Boc chemistry.
- Each amino acid is activated (e.g., using HBTU/HOBt or DIC) and coupled.
Washing Steps: Excess reagents and side-products are removed after each step.

🔄 2. Deprotection:

Fmoc group is removed using 20% piperidine in DMF.
This exposes the amine group of the growing peptide for the next coupling.

🧬 3. Chain Elongation:

The peptide sequence for Icatibant (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg) is built step-by-step.

🔓 4. Cleavage from Resin & Side Chain Deprotection:

Once complete, the full peptide is cleaved from the resin using TFA (trifluoroacetic acid) and scavengers.
This step also removes side-chain protecting groups.

💧 5. Purification:

Crude peptide is purified using Reverse Phase HPLC (RP-HPLC) or Preparative HPLC.
Target purity is typically ≥98%.

🧂 6. Acetate Salt Formation:

The purified peptide is converted to its acetate form by treatment with acetic acid.

🧊 7. Lyophilization (Freeze Drying):

The acetate form is lyophilized into a dry powder, enhancing its shelf life and stability.

🏭 Manufacturing at Swapnroop:

Uses state-of-the-art peptide synthesizers
Strict control over:
- Coupling efficiency
- Impurities
- Peptide folding (if needed)
Complies with ICH, WHO-GMP, and USFDA guidelines

✅ Summary of Key Steps:

Step	Description
Peptide Assembly	SPPS (Fmoc strategy)
Cleavage & Deprotection	TFA treatment

Q6: How are ICATIBANT ACETATE dosage forms manufactured by Swapnroop Drugs and Pharmaceuticals? 💉🏭

ICATIBANT ACETATE is primarily formulated as a sterile injectable solution for subcutaneous (SC) administration. Swapnroop Drugs & Pharmaceuticals manufactures this dosage form under aseptic and GMP-compliant conditions, with precise attention to peptide stability and sterility.

🧪 Formulation Process for Injection:

1️⃣ API Dissolution:

The purified Icatibant Acetate API is dissolved in sterile water or a buffer solution (often citric acid/sodium chloride for pH adjustment).
The pH is adjusted to around 5.5–7.0 to ensure stability.

2️⃣ Sterile Filtration:

The solution is filtered using 0.22 µm sterile filters to remove any microbial contaminants.

3️⃣ Filling & Sealing:

The sterile solution is filled into pre-sterilized glass vials or pre-filled syringes under laminar airflow in a Grade A aseptic environment.
Sealing is done with rubber stoppers and aluminum caps.

4️⃣ Lyophilization (if applicable):

Some formulations may be freeze-dried (lyophilized) for extended shelf life.
Reconstitution is done with sterile water before injection.

5️⃣ Inspection & Labeling:

Filled containers are visually inspected for particulates and integrity.
Each unit is labeled, serialized, and packed per regulatory requirements.

⚗️ Excipients Typically Used:

Water for Injection (WFI)
Citric acid or acetate buffer
Sodium chloride (for isotonicity)
Acetic acid (for pH adjustment)

📦 Final Product Characteristics:

Form	Details
Solution for Injection	Clear, colorless, sterile liquid
Dosage Strength	Commonly 30 mg/3 mL (10 mg/mL)
Route of Admin	Subcutaneous (SC)
Packaging	Pre-filled syringe or single-use vial
Storage	2–8°C (Refrigerated), Protect from light

🏭 Swapnroop's Advantages:

Peptide formulation expertise 💉
GMP-compliant injectable facility 🧪
Stability-tested packaging and shelf life 🕒

Q7: What is the appropriate dosage form of ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals? 💊🧬

✅ The appropriate and globally accepted dosage form of Icatibant Acetate is:

🔹 Sterile, preservative-free solution for subcutaneous injection (SC)

📌 Standard Clinical Use Formulation:

30 mg in 3 mL solution (10 mg/mL)
Supplied in a pre-filled syringe for self-administration or by a healthcare professional

💡 Why This Dosage Form?

💉 Feature	Benefit
Subcutaneous Injection	Enables rapid absorption during HAE attacks
Pre-filled Syringe	Facilitates easy and quick self-injection
Preservative-free	Reduces risk of allergic reactions
Aqueous Solution	Fast onset of action (within 30–90 minutes)
Single-dose	Ensures accurate and complete dosing

🧬 Special Considerations:

The peptide nature of Icatibant requires injection due to poor oral bioavailability.
Not suitable for oral, transdermal, or rectal delivery due to degradation in GI tract.

Q8: When should ICATIBANT ACETATE API manufactured by Swapnroop Drugs and Pharmaceuticals be taken? ⏱️💉

ICATIBANT ACETATE is not a routine or daily medication. Instead, it is used on-demand to treat acute attacks of Hereditary Angioedema (HAE).

🧬 When to Administer:

✅ Administer ICATIBANT Acetate as soon as an HAE attack begins, especially if swelling affects the:

Face
Throat
Abdomen
Limbs

🚨 In Case of Laryngeal (Throat) Attacks:

Immediate injection is critical as it can be life-saving.
Seek emergency care after self-injection due to potential airway compromise.

💉 Dosing Guidance:

Patient Group	Dose	Timing
Adults (≥18)	30 mg SC (single dose)	At onset of attack
Re-dosing	1 additional dose may be given after 6 hours if symptoms persist (Max: 3 doses in 24 hrs)

🛑 When NOT to Use:

Preventively (not for prophylaxis)
In mild attacks that resolve spontaneously
Without clear signs of HAE flare (diagnosis is essential)

🧠 Reminder:

This is a symptom-triggered medication, not taken daily. Swapnroop’s Icatibant Acetate is fast-acting, making early administration key to stopping attacks quickly and effectively.

Q9: What are the effects and side effects of ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals? ⚖️💉

✅ Primary Effects (Therapeutic):

Effect	Mechanism
Relief from swelling	Blocks bradykinin B2 receptor, reducing fluid leakage
Pain reduction	Stops pain associated with tissue edema
Airway protection	Prevents or reverses throat swelling during HAE

😌 Clinical Benefit:

Relief typically begins within 30 minutes
Most patients fully recover within 2–5 hours

⚠️ Common Side Effects (usually mild and temporary):

💢 Symptom	📌 Frequency	🧬 Notes
Injection site reaction	Very common (up to 97%)	Redness, pain, swelling, itching — resolves in hours
Fever	Uncommon	Mild and transient
Nausea	Less common	May occur with abdominal attacks
Dizziness	Rare	Usually mild
Fatigue	Occasionally reported	Short-lived

🚨 Rare but Serious Reactions:

Hypersensitivity / Allergic reaction
Injection site infection (if aseptic technique fails)
Worsening of airway symptoms if used too late during an attack

🛑 Precautions:

Use with caution in pregnant or breastfeeding women
Not recommended in children under 18 without clinical supervision
Avoid combining with ACE inhibitors (as they also affect bradykinin pathways)

Q10: How is ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals tested? 🔬✅

To ensure purity, potency, safety, and compliance, ICATIBANT ACETATE undergoes rigorous testing at multiple stages during and after manufacturing at Swapnroop Drugs & Pharmaceuticals.

🧪 Stages of Testing:

1️⃣ Raw Material Testing:

Identity, purity, and quality of all starting materials (amino acids, solvents, reagents)
Compliance with pharmacopeial or internal specifications (e.g., IP, BP, EP, USP)

2️⃣ In-Process Testing:

Peptide elongation monitoring (using HPLC or LC-MS)
Coupling and deprotection efficiency
Resin cleavage verification
Solvent purity checks

3️⃣ Final API Testing:

Ensures the peptide meets ICH Q7 and GMP quality standards

🔍 Key Final Tests Performed:

Test	Purpose	Method
Appearance	Check for color, clarity	Visual inspection
Identification (ID)	Confirm correct peptide sequence	HPLC, MS, IR, NMR
Assay (Potency)	Confirm correct strength (≥98%)	HPLC or LC-MS
Related Substances (Impurities)	Ensure minimal degradation products	HPLC or UPLC
Residual Solvents	Detect any remaining organic solvents	GC (per ICH Q3C)
Water Content (Karl Fischer)	Confirm proper moisture level	KF Titration
pH of solution	Critical for injection safety	pH meter
Bacterial Endotoxins (BET)	Ensure no pyrogenic contamination	LAL Test
Sterility	Must be sterile for injection	Per USP <71>
Peptide Purity	Confirm identity and quality	RP-HPLC
Specific Rotation	Confirms stereochemical integrity	Polarimetry

🧴 Finished Product Testing (Dosage Form):

Volume, clarity, sterility, leak test, and container-closure integrity
Stability studies as per ICH Q1A(R2) guidelines

Q11: What tests are performed on ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals? 📋🧬

The following critical tests are routinely performed on the API and formulation of Icatibant Acetate:

📌 Summary of Major Tests on API & Dosage Form:

Test Name	Why It’s Performed	Regulatory Standard
Identity (IR, MS, HPLC)	Confirms chemical structure	ICH Q6A
Assay / Potency	Verifies correct API content	USP/EP/ICH
Impurities / Related Substances	Ensures peptide is not degraded or impure	ICH Q3A, Q3B
Water content	Confirms correct moisture level	USP <921>
Residual Solvents	Checks for toxic solvents (e.g., DMF, DCM)	ICH Q3C
Sterility Test	Ensures product is microbe-free	USP <71>
Bacterial Endotoxins	Ensures absence of fever-causing endotoxins	USP <85>
pH measurement	Confirms physiological compatibility	USP <791>
Appearance & Clarity	Visual safety parameter	In-house/USP
Container Closure Integrity	Ensures no leaks or breaches	USP <1207>
Stability Testing	Confirms shelf life under stress conditions	ICH Q1A(R2), Q1B
Peptide Mapping / Sequencing	Confirms the correct order of amino acids	LC-MS/MS

🧠 Swapnroop’s Quality Focus:

Advanced analytical development labs
Stringent QA/QC protocols
Regulatory documentation support (DMF, CTD)

Q12: What are the challenges in manufacturing ICATIBANT ACETATE API by Swapnroop Drugs and Pharmaceuticals? 🧪⚙️

Manufacturing ICATIBANT ACETATE API is complex due to its peptide nature, which demands precision, purity, and advanced synthesis techniques.

⚠️ Key Manufacturing Challenges:

1️⃣ Solid Phase Peptide Synthesis (SPPS) Complexity 🔄

Icatibant is a decapeptide (10 amino acids), requiring:
- Precise sequential coupling
- High-efficiency Fmoc-protected amino acids
Risk of incomplete reactions, leading to impurities or deletion sequences.

2️⃣ Purity & Yield Optimization 🎯

Impurity profile must meet ICH Q3A/B limits.
Loss during synthesis, cleavage, and purification leads to:
- Lower yields
- Higher cost of goods (COGs)

3️⃣ Purification Difficulties 🚿

Requires high-resolution preparative HPLC or chromatography.
Peptides often co-elute with closely related impurities.
Purification solvents and buffers must be residue-free.

4️⃣ Moisture and Temperature Sensitivity 🌡️💧

Peptide APIs are hygroscopic and can degrade if not stored/handled correctly.
Need for strict environmental controls (humidity, temperature).

5️⃣ Residual Solvents & Reagents 🧪

SPPS uses solvents like DMF, DCM, piperidine — all must be removed thoroughly.
ICH Q3C compliance is mandatory.

6️⃣ Analytical Challenges 📊

Requires advanced testing:
- Peptide mapping
- LC-MS
- NMR for structural confirmation

🧬 Swapnroop’s Approach:

Employs automated synthesizers, in-process controls
State-of-the-art purification and lyophilization facilities

Q13: What are the challenges in manufacturing ICATIBANT ACETATE dosage forms by Swapnroop Drugs and Pharmaceuticals? 💉🏭

Formulating ICATIBANT ACETATE into a stable injectable dosage form involves regulatory, technical, and logistical complexities.

⚠️ Dosage Form Manufacturing Challenges:

1️⃣ Peptide Stability in Solution 🧬💧

Icatibant is susceptible to:
- Hydrolysis
- Oxidation
- Aggregation
Requires careful pH adjustment (5.5–7.0) and antioxidants.

2️⃣ Sterility Assurance 🔬

Final dosage must be completely sterile and pyrogen-free.
Requires:
- Aseptic filling
- Sterile filtration (0.22 µm)
- Class A cleanroom conditions

3️⃣ Container-Closure Integrity 🧴

Packaging in pre-filled syringes or glass vials must:
- Maintain sterility
- Prevent light and oxygen exposure
- Be compatible with the peptide (no adsorption or leaching)

4️⃣ Injection Site Tolerability 💢

Needs isotonic formulation (sodium chloride)
Excipients must be non-irritant and preservative-free

5️⃣ Batch-to-Batch Consistency 📦

Small variations in pH, excipients, or peptide concentration can affect:
- Efficacy
- Shelf life
- Patient safety

6️⃣ Cold Chain Logistics ❄️🚚

Product must be stored at 2–8°C (refrigerated)
Requires cold chain management through transport and storage

🏭 Swapnroop's Capabilities:

GMP-certified sterile facilities
Controlled filling lines
Stability-tested packaging and regulatory-compliant documentation

Q14: What are the storage conditions for ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals? ❄️📦

Proper storage of ICATIBANT ACETATE, both API and finished injectable, is crucial to maintaining stability, potency, and safety.

🧪 API Storage Conditions:

Condition	Specification
Temperature	2–8°C (Refrigerated)
Protection	Keep in original container, tightly sealed
Humidity	Store in dry, moisture-controlled environment
Light	Protect from direct sunlight or UV exposure
Container	Use HDPE or amber glass containers with desiccants

💉 Finished Dosage (Injection) Storage:

Form	Storage
Pre-filled Syringe or Vial	Refrigerate at 2–8°C; do not freeze
Opened vial	Use immediately after opening
Shelf stability	Must not be exposed to >25°C for extended periods

⚠️ Stability Risks:

Freezing can cause precipitation
Excessive heat causes degradation or loss of potency
Moisture affects peptide integrity

Q15: What is the packaging for ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals? 📦💉

Packaging is designed to protect the product from contamination, degradation, and light exposure, while ensuring user convenience.

🧪 API Packaging:

Packaging Type	Description
Primary	Amber glass or HDPE bottle with Teflon-lined cap
Secondary	Aluminum foil pouch or vacuum-sealed polybag
Labeling	Product name, batch no., retest date, storage temp, manufacturer
Tamper-evidence	Seals or shrink bands to prevent unauthorized access

💉 Finished Dosage Form (Injection) Packaging:

Format	Components
Single-dose 3 mL pre-filled syringe	✅ Glass syringe with rubber stopper ✅ Protective plunger ✅ Needle cover
Glass vial (multi-dose)	✅ Type I glass vial with flip-off cap ✅ Rubber stopper ✅ Aluminum seal
Secondary packaging	✅ Sterile blister pack ✅ Carton with patient information leaflet
Outer packaging	✅ Cold chain-compliant box with insulation and gel packs (for transport)

Q16: What is the shelf life of ICATIBANT ACETATE manufactured by Swapnroop Drugs and Pharmaceuticals? ⏳🧊

Shelf life depends on form, storage, and container conditions — defined by ICH stability data.

🧪 API Shelf Life:

Condition	Shelf Life
2–8°C (sealed container)	24 months from manufacturing date
Opened or exposed	Use within 3–6 months, under validated controls
Accelerated stability (25°C ± 2°C / 60% RH ± 5%)	~6 months (for stress testing only)

💉 Finished Injection Shelf Life:

Format	Shelf Life
Pre-filled syringe (sealed)	18–24 months (refrigerated)
Opened vial/syringe	Use immediately; discard unused portion
If stored at >25°C	Shelf life significantly reduced; potency loss may occur

📋 Stability Studies:

Swapnroop performs:

Real-time & accelerated stability studies
As per ICH Q1A(R2), Q1B guidelines
With full data on degradation, potency retention, and microbial safety