Active Pharmaceutical Ingredients
Active pharmaceutical ingredients (APIs) are the components of a drug that produce its intended therapeutic effect. When formulating syrups, careful consideration must be given to the selection of APIs.
Azithromycin syrup
paracetamol syrup
Common APIs Used in Syrups
Some of the most commonly used APIs in syrup formulations include:
- Analgesics like acetaminophen and ibuprofen to relieve pain
- Antitussives like dextromethorphan to suppress coughs
- Expectorants like guaifenesin to loosen mucus
- Antihistamines like diphenhydramine for allergy relief
- Decongestants like pseudoephedrine to relieve nasal congestion
- Antibiotics like amoxicillin to treat infections
The choice of API depends on the intended therapeutic use of the syrup. Most syrups contain just one API, but some may combine multiple active ingredients.
paracetamol syrup
Azithromycin syrup
Solubility Considerations
A key factor in selecting APIs for syrups is solubility. Syrups are aqueous solutions, so the API must have sufficient solubility in water for the intended dose. APIs with low aqueous solubility may need solubilizing agents added to the formulation.
For ionizable APIs, solubility depends greatly on pH. The syrup's pH may need adjustment to keep the API dissolved. Syrups generally have a pH between 4-6 for optimal API stability and palatability.
Azithromycin syrup
paracetamol syrup
Stability
Active ingredients in syrups can degrade via hydrolysis, oxidation, temperature, and other factors. The manufacturer must test API stability under typical storage conditions and shelf life.
Certain excipients like antioxidants and chelating agents may improve API stability. The container closure system also impacts stability. Refrigerated storage may be needed for some syrups.
API stability data guides the labeled expiration date and storage conditions for the final syrup product. Careful API selection and formulation are crucial for an optimal shelf life.
Excipients
Excipients play a critical role in pharmaceutical syrup formulations. They help impart important physical properties to the syrup, mask any unpleasant taste of the active pharmaceutical ingredient (API), and improve stability.
Some common excipients used in syrups include:
- **Viscosity modifiers**
- These excipients help modulate the viscosity and flow behavior of the syrup. Examples include glycerin, sorbitol, sucrose, and carboxymethylcellulose sodium. They help provide an ideal thickness and mouthfeel.
- **Sweeteners**
- Sweeteners like sucrose, fructose, or artificial sweeteners are added to mask any bitter taste of the API and improve palatability. The choice and combination of sweeteners can impact properties like viscosity, stability, and sweetness perception.
- **Preservatives**
- Preservatives prevent microbiological contamination and spoilage of the syrup. Common preservatives include methylparaben, propylparaben, potassium sorbate, and sodium benzoate. The level of preservative is carefully optimized to provide efficacy while ensuring patient safety.
- **Flavors & colors**
- Flavoring agents like lemon oil or orange flavor and permitted coloring agents are often added to improve the esthetics and taste masking of syrups.
The choice and levels of excipients can significantly impact the pharmaceutically relevant properties of the final syrup product like viscosity, palatability, microbial quality, and API stability. Excipient compatibility and optimization is a critical step in developing stable and patient-centric syrup formulations.
Syrup Manufacturing Process
The manufacturing process for pharmaceutical syrups involves several key steps to produce a homogeneous, stable, and safe final product.
Mixing and Dissolving APIs
The active pharmaceutical ingredients (APIs) are first accurately weighed and added to the syrup base in the desired concentration. The APIs are dissolved through mechanical mixing and agitation. High shear mixers are often used to ensure proper dispersion and dissolution of the APIs. Factors like temperature, pH, and mixing time must be controlled to achieve optimal dissolution.
Filtration
Once dissolved, the syrup solution goes through filtration to remove any undissolved particles or impurities. Different filtration methods like vacuum, pressure, or membrane filtration can be utilized based on the viscosity and composition of the syrup. Proper filtration helps improve the clarity, stability and shelf life of the final product.
Homogenization
The filtered syrup solution then undergoes homogenization to reduce the particle size and evenly distribute the ingredients. Homogenization is done using equipment like high-pressure homogenizers. It improves the consistency, texture, and mouthfeel of the final syrup.
Filling/Packaging
The final step is aseptic filling and packaging of the homogeneous syrup solution into bottles, sachets or other packaging. Accuracy of fill volumes and integrity of packaging material is crucial. The filled syrups go through final checks before release. Automated filling and packaging lines are commonly used for efficiency and quality control.
Proper control and validation of the manufacturing process is key to producing a high-quality pharmaceutical syrup at commercial scale.
Quality Control Testing
Quality control testing is a critical part of pharmaceutical syrup manufacturing to ensure the final product meets specifications and is safe for human consumption. Some of the key tests conducted are:
Viscosity Testing
- Measures the thickness and flow characteristics of the syrup
- Important to ensure proper pouring and dosing of the medication
- Typically measured using a viscometer, which determines the syrup's resistance to flow
- Results compared to established viscosity specifications
Microbial Testing
- Screens for contamination by bacteria, mold, yeast
- Usually involves taking samples and culturing them on growth media
- Checks for pathogens like E. coli, Salmonella, Staphylococcus
- Ensures product sterility and lack of bioburden
Chemical Assay
- Verifies the proper amount of active pharmaceutical ingredient (API) is present
- Uses analytical techniques like high-performance liquid chromatography
- Measures concentration of API against a reference standard curve
- Confirms API content meets requirements
pH Testing
- Measures acidity/alkalinity of the syrup
- Can affect solubility, stability, and taste of the product
- Performed using a pH meter on samples
- Results must fall within established pH specification range
Proper quality control testing ensures the final syrup product is safe and effective for patient use. Failures can lead to recalls, health hazards, or lack of efficacy if out of specification.
Regulations
The manufacturing of pharmaceutical syrups is a highly regulated process. Companies must follow Good Manufacturing Practices (GMP) guidelines and comply with rules from regulatory agencies like the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).
Good Manufacturing Practices
GMP guidelines provide a framework of minimum requirements for the methods, facilities, and controls used in manufacturing, processing, packing, and holding drugs. They aim to ensure that syrups are produced consistently and controlled according to quality standards. GMP regulations address qualifications and training, buildings and facilities, equipment, control of components and packaging materials, production and process controls, packaging and labeling controls, holding and distribution, laboratory controls, records and reports, and returned and salvaged products.
Regional Regulations
In the United States, pharmaceutical syrups must meet FDA requirements. The FDA inspects manufacturing facilities and reviews data to ensure safety, effectiveness, quality, and accurate labeling. Companies must register facilities engaged in pharmaceutical production and list all drugs made at each facility. The FDA also expects compliance with current Good Manufacturing Practices.
In Europe, the EMA works with EU members to oversee medicines regulation. Manufacturers must comply with EU good manufacturing practice principles and guidelines. The EMA can inspect sites and issue good manufacturing practice certificates. Each country also has its own national competent authority responsible for regulating pharmaceutical products.
Regulations also exist in other countries and regions like Canada, Australia, Japan, and emerging markets. Companies looking to sell globally must understand and adapt to a complex world of regulatory requirements. With increased outsourcing and globalization, cooperation between international regulators continues to grow.
Facility and Equipment
Manufacturing pharmaceutical syrups requires specialized equipment and facilities to ensure product quality and safety. Some key considerations include:
**Manufacturing Equipment**
- Stainless steel tanks and pipes should be used to mix and transfer ingredients and bulk syrup. Stainless steel prevents corrosion and minimizes contamination.
- Mixers, blenders, homogenizers, and mills are needed to properly combine ingredients and achieve uniform particle sizes in suspensions.
- Filtration systems remove impurities and clarify the syrup. Multiple filtration steps are often used.
- Filling machines accurately dispense the syrup into bottles, jars or other final packaging. Automated filling lines improve efficiency.
- Labeling and sealing equipment prepares the final packaged product. Track and trace systems may be implemented.
**Cleanroom Standards**
- Syrup manufacturing facilities should meet cGMP and ISO classifications for cleanrooms. Higher ISO classes (7 or 8) are ideal for sterile syrups.
- Air filtration, room pressurization, gowning procedures and cleaning protocols must be in place to control airborne particulates and microbial contamination.
- Regular environmental monitoring should be performed to ensure cleanroom conditions are maintained.
- Dedicated gowning rooms separate the manufacturing space from lower hygiene areas. Personnel follow hand washing and gowning procedures.
Proper equipment selection, facility design, and contamination controls give pharmaceutical syrups the high quality expected of human drugs. Regulators closely inspect facilities and manufacturing processes.
Trends and Innovations
The pharmaceutical syrup manufacturing industry continues to evolve with new technologies and innovations. Some key trends shaping the future of syrup production include:
**Flavored and specialized syrups**
- There is growing demand for flavored syrups, especially for pediatric populations, that taste better and mask unpleasant drug flavors. Companies are developing fruit and sweetener flavor systems to improve palatability. Specialized syrups are also emerging, like viscosity-adjusted syrups that aid swallowing difficulties.
**Modified release syrups**
- Modified release syrup formulations are being introduced to control the drug release rate. These include sustained release, delayed release, and extended release syrups. Manufacturers use technologies like ion exchange resins, micro-encapsulation, and lipid-based systems to modify drug delivery.
**Automation**
- Automated systems are being implemented to improve efficiency, accuracy, and compliance. Syrup production lines now integrate automated dispensing, inspection, and packaging. Robotic arms can handle repetitive tasks like material transfer. Inline quality control checks using sensors reduce human errors. Automation also aids compliance with electronic batch records.
These innovations allow pharmaceutical companies to create novel syrup products, scale up production, reduce costs, and meet quality standards more easily. However, implementing new technologies requires significant investment and expertise. Overall, the industry is moving towards more customized, controlled, efficient, and compliant manufacturing processes.
Common Issues and Solutions
Pharmaceutical syrup manufacturing comes with some common challenges that manufacturers need to be aware of and implement strategies to prevent.
Microbial Contamination
Microbial contamination is a significant risk in syrup production that can lead to product recalls or consumer illness. Suggested ways to prevent microbial contamination include:
- Careful cleaning and sanitization of manufacturing equipment
- Ensuring raw materials have been sufficiently tested
- Working in cleanroom environments
- Following strict hygiene protocols for staff
- Incorporating microbial retention filters on lines
- Conducting regular microbial testing at various stages
Crystal Formation
Crystal formation can occur when syrup ingredients fall out of solution. This affects visual quality and can cause dosing issues. Ways to prevent crystals include:
- Careful selection of excipients for solubility
- Adding stabilizing or solubilizing agents
- Maintaining proper storage and distribution temperatures
- Agitation during storage to prevent settling
- Built-in microfiltration steps
Separation
Syrup separation happens when the syrup's components split, causing visual and dosing problems. To prevent separation:
- Select optimal ingredient ratios and compatible excipients
- Incorporate suspending, stabilizing, and emulsifying agents
- Use homogenization during processing
- Ensure proper viscosity
- Carry out stability studies to confirm shelf life
With careful manufacturing processes and testing, these common issues in syrup production can be prevented.
Conclusion
Pharmaceutical syrups play an important role in making oral drug administration more palatable and effective, especially for children and the elderly. The manufacturing process requires careful attention to ensure product quality and safety.
Key steps include creating a uniform syrup base, dissolving or suspending the active pharmaceutical ingredients, testing and quality control, and sterile bottling. At each stage, factors like ingredient compatibility, temperature, pH, viscosity, and microorganisms must be monitored and controlled. Proper equipment cleaning and sanitization between batches is also critical.
Stringent regulations guide syrup manufacturing to protect consumers. Facilities must adhere to cGMP and local guidelines. Detailed protocols, training, and documentation ensure standards are met consistently. Any deviations can impact syrup potency or stability.
By leveraging technology and expertise, manufacturers can optimize efficiency and output. However, quality must remain the top priority. Syrups that are contaminated, ineffective, or unstable can pose major health risks. Ensuring safety and efficacy from raw materials selection to final release testing is paramount
With careful attention to detail and quality, pharmaceutical syrups can safely provide patients, especially children, with the intended therapeutic effects. Responsible manufacturing principles help ensure these important oral liquid medicines are produced to the highest standards.
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Product List - Liquid Injections
| Product Name |
Strength |
| Vitamin B1 injection |
100mg: 2ml |
| Vitamin B6 Injection |
0.1g: 2ml |
| Vitamin B12 injection |
0.5mg:1ml |
| VIT-B Complex injection |
2ml |
| Tri B-inj B1-100mg+B2-100mg+B12-1000mcg |
3ml |
| Vitamin C injection |
0.5g:2ml |
| VITAMIN K1 injection |
10mg:1ml |
| Dexamethasone Na phosphate injection |
4mg: 1ml |
| Dexamethasone Na phosphate injection |
8mg: 2ml |
| Diclofenac Sodium Injection |
75mg:3ml |
| Metoclopramide hydrochloride injection |
10mg:2ml |
| Metoclopramide hydrochloride injection |
5mg:1ml |
| Iron Sucrose IV Injection |
100mg:5ml |
| Iron Dextran Injection |
100mg:2ml |
| Promethazine Hydrochloride Injection |
50mg:2ml |
| Gentamycin sulfate injection |
40mg:2ml |
| Gentamycin sulfate injection |
80mg:2ml |
| Furosemide Injection |
20mg:2ml |
| Aminophylline Injection |
250mg:10ml |
| Paracetamol injection |
150mg:1ml |
| Paracetamol injection |
300mg:2ml |
| Paracetamol injection |
500mg:4ml |
| Paracetamol injection |
600mg:4ml |
| Paracetamol injection |
750mg:5ml |
| Diazepam injection |
5mg/1ml |
| Diazepam injection |
10mg:2ml |
| Diazepam injection |
5mg/1ml |
| Diazepam injection |
10mg:2ml |
| Oxytocin Injection |
5 iu/1ml |
| Oxytocin Injection |
10 iu / 1ml |
| Chlorphenamine Maleate Injection |
10mg:1ml |
| Hyoscine Butylbromide(Buscopan)Injection |
20mg:1ml |
| Lidocaine Hydrochloride injection |
10ml：0.2g |
| Methotrexate for Injection |
50mg:2ml |
| ENOXAPARIN SODIUM Prefilled syringe |
40MG/0.4ML |
| ENOXAPARIN SODIUM Prefilled syringe |
60MG/0.6ML |
| ENOXAPARIN SODIUM Prefilled syringe |
80MG/0.8ML |
| Adrenaline(Epinephrine HCL)Injection |
1mg:1ml |
| Testosterone 250mg:1ml |
250mg:1ml |
Product List - Vial Injections
| Product Name |
Strength |
| Omeprazol 40 mg IV VIAL |
10ml or 5ml |
| Pantoprazole Sodium for Injection |
40mg |
| Lansoprazole for Injection |
30 mg |
| Ceftriaxone 1gm/10ml IV VIAL |
+10ml water |
| Ceftriaxone 1gm/10ml VIAL |
+Lidocain 1% |
| Ceftriaxone IM/IV VIAL |
500mg/15 ml |
| Ampicillin Na VIAL |
0.5 g/Vial |
| Ampicillin Na VIAL |
1g/Vial |
| Cefotaxime Sodium for VIAL |
1g/Vial |
| Ceftazidime For I.M/I.V VIAL |
1g/Vial |
| Cefepime For I.M/I.V VIAL |
1g/Vial |
| Meropenem VIAL Injection |
1g/20ml/Vial |
| Procaine Penicillin(0.4mega/7ml) |
400.000 U/7ml |
| Procaine Penicillin(0.6mega/7ml) |
600.000 U/7ml |
| Procaine Penicillin(1.2mega/7ml) |
800.000 U/7ml |
| Procaine Penicillin (0.8mega/7ml) |
1200.000 U/7ml |
| Benzathine Penicillin for Injection |
1.2mega/7ml |
| Vancomycin Hcl injection 500mg |
500mg/Vial |
| Vancomycin Hcl injection 500mg |
1g/Vial |
| Heparin Sodium Injection |
5ml:5000 units |
| Heparin Sodium Injection |
5ml:25000 units |
| Amoxicillin Na and Clavulanate Potassium for Inj(augmentin) |
G Powder 1.2 |
| Amoxicillin Na and Clavulanate Potassium for Inj(augmentin) |
G Powder 0.6 |
| lyophilized Hydrocortisone Na Succinate |
3ml:0.1gm |
| aseptic lyophilized Hydrocortisone Na Succinate |
7m:0.1gm |
| Phenobarbital Sodium Injection |
1ml：0.1g |
| Piperacillin Sodium and Tazobactam Na for Inj |
4.5g |
Product List - IV INFUSION
| Product Name |
Strength |
| Paracetamol 1G IV infusion |
100ml glass bottle |
| Metronidazole 500mg IV infusion |
100ml glass bottle |
| Ciprofloxacine 200mg IV infusion |
20ml plastic bottle |
| 0.9% Na Chloride IV Inj |
500ml plastic bottle |
| 5% Glucose Injection |
250ml:12.5g,500ml:25g |
| 10% Glucose Injection |
250ml:12.5g,500ml:25g |
| Sodium Lactate Ringer`s Inj |
500ml Plastic Bottle |
| 5% Glu + 0.9% Na Chlorid inj 250ml: |
Glu 12.5g,NaCl 2.25g |
| 5% Glu + 0.9% Na Chlorid inj 500ml: |
Glu 25g,NaCl 4.5g |
| 10% Glu + 0.9% Na Chlorid inj 250ml: |
Glu 25g,NaCl 2.25g |
| 10% Glu + 0.9% Na Chlorid inj 500ml: |
Glu 50g,NaCl 4.5g |
| Mannitol injection |
250ml:50g P Bottle |
Product List - SYRUP
| Product Name |
Strength |
| Amoxicillin 125mg + Clavulanic Acid 31.5mg |
100 ml glass Bottle |
| Amoxicillin 250mg + Clavulanic Acid 62.5mg |
100 ml glass Bottle |
| Amoxicillin 400mg + Clavulanic Acid 75mg |
100 ml glass Bottle |
| Azithromycine 100mg |
15ml 1bottle/Box |
| Metronidazole 125mg |
100 ml glass Bottle |
| Metronidazole 250mg |
100 ml glass Bottle |
| Amoxicillin 125 mg |
100 ml glass Bottle |
| Amoxicillin 250 mg |
100 ml glass Bottle |
| Paracetamol syrup 250mg/5ml |
250mg/5ml syrup |
| Ibuprofen Dry Suspension 100mg/5ml |
100ml Suspension |
Product List - TABLETS
| Product Name |
Strength |
| Azithromycine 500mg Tab(3 tabs) |
3 tablets X 1 blister |
| Metronidazole 500mg Tab(14 tabs) |
7 tablets X 2 blisters |
| Ciprofloxacine 500mg TAB(10 tabs) |
10 tablets X 1 blister |
| Amoxicillin 250mg + Clavulanic Acid 125mg(14 tabs) |
7 tablets x 2 blister |
| Amoxicillin 500mg + Clavulanic Acid 125mg(14 tabs) |
7 tablets x 2 blister |
| Amoxicillin 875mg + Clavulanic Acid 125mg(14 tabs) |
7 tablets x 2 blister |
| Nitrofurantoin 100mg Tablets |
10 tablets X 1 blister |
| Aspirin Enteric-coated 500mg |
10 tablets X 1 blister |
| Paracetamol 500mg |
10 tablets X 1 blister |
| Ibuprofen 400mg |
10 tablets X 1 blister |
| Diclofenac Na 400mg |
10 tablets X 1 blister |
| Diclofenac 50mg + Paracetamol 500mg |
10 tablets X 1 blister |
| Folic acid 5mg Tab |
10 tablets X 1 blister |
| Ciprofloxacin Tablets |
10 tablets X 1 blister |
| Doxycycline 100mg Tab |
10 tablets X 1 blister |
| Meloxicam 15mg Tab |
10 tablets X 2 blisters |
| Fluconazole 150mg Tab |
10 tablets X 2 blisters |
| Simvastatin 40mg Tab |
10 tablets X 2 blisters |
| Prednisolone 5mg Tab |
10 tablets X 2 blisters |
| Spiramycin 750,000 unit Tab |
10 tablets X 2 blisters |
| Spiramycin 1,500,000 unit Tab |
10 tablets X 2 blisters |
Product List - CAPSULES
| Product Name |
Strength |
| Amoxicillin 500mg(16 Capsules) |
8 cap X 2 blisters |
| Ampicillin Capsules |
10 cap X 2 blisters |
| Cloxacillin Na Capsules |
10 cap X 2 blisters |
| Piroxicam Capsule |
10 cap X 2 blisters |
| Tetracyline 250 mg Capsule |
10 cap X 2 blisters |
| Oxytetracycline 250mg Capsule |
10 cap X 2 blisters |
| Spiramycin 375,000 unit Cap |
10 cap X 2 blisters |
| Indomethacin 25mg Capsule |
10 cap X 2 blisters |
Product List - Suppository
| Product Name |
Strength |
| Paracetamol 125mg suppository |
5 Supp x 2 blister |
| Paracetamol 250mg suppository |
5 Supp x 2 blister |
| Policresulen Vaginal 90mg Suppository |
4 Supp x 2 blister |
| Chlorhexidine Acetate 20mg Supp |
5 Supp x 2 blister |
| Miconazole Nitrate Vaginal 100mg Supp |
5 Supp x 2 blister |
| Clotrimazole Vaginal 150mg Supp |
5 Supp x 2 blister |
| Metronidazole Vaginal 500mg Supp |
5 Supp x 2 blister |
| Indomethacin 500mg Supp |
5 Supp x 2 blister |
