At BOC Sciences, we value the complexity of the drop formulation as well as sterility. With years of industry experience, we use advanced technology and meticulous quality control processes to develop drop formulations that meet the highest industry standards.
Drops, which include eye drops, nose drops and ear drops, play a key role in delivering drugs in a convenient, non-invasive manner. Eye drops means a sterile aqueous or oil-based clarifying solution, suspension or emulsion made of a drug and suitable excipients for use in eye drops. Eye drops are local drugs, which have bactericidal, anti-inflammatory, pupil dilation, pupil contraction, anesthesia and other effects on the eye.
Nasal administration can effectively avoid the liver first pass effect, but a variety of metabolic enzymes in the nasal mucosa can cause "false first pass effect", which affects the stability of the drug. The enzyme activity of the nasal cavity and the muco-ciliary clearance system all affect the efficiency of drug delivery through the nose. Nasal drops are the simplest form of nasal administration, that is, a solution of the drug (including suspension) is dropped directly into the nasal cavity. The nasal potion should be isotonic, pH neutral, and viscosity similar to that of nasal secretions made of methanol.
Ear drops are liquid pharmaceutical preparations that are dropped into the ear canal, generally using water, ethanol, glycerin, propylene glycol, polyethylene glycol, etc., as solvents to clean, reduce inflammation and astringent the ear canal.
For sterile liquid preparations, a 0.22μm filter membrane is usually used for filtration and removal of bacteria. Autoclaving is commonly used to sterilize containers and formulation ingredients to maintain a sterile production environment. When filtration or autoclaving may affect the stability of the active pharmaceutical ingredient (API), irradiation can be used to sterilize the product without overheating or filtering it, thereby maintaining the integrity of the formula.
Different from solution type drops, suspension type drops of the raw material suspended in the solution, usually can not be filtered through the filter membrane to remove bacteria, so often use aseptic production and sterilization production two different production methods.
Aseptic production: Since the API cannot be filtered through the filter membrane to remove bacteria, the excipients are usually dissolved in water for injection during production, and the excipient solution is prepared after filtration. Then the sterile API treated in advance is added to the excipient solution, and the finished product is filled under aseptic conditions after mixing and homogenizing.
Sterilization production: Sterilization production usually includes two different production methods, namely concentrated solution sterilization method and dilute mix sterilization method, the difference between the two methods is the type of sterilization raw materials and sterilization volume. For the concentrated solution sterilization method, the API and part of the excipients are usually dispersed in part of the water for injection for sterilization, and other excipients and water for injection are aseptically filtered through the filter membrane, and then the sterilized concentrated solution containing the API is mixed with the part of the excipient solution after sterile filtration, and the finished product is filled under sterile conditions after homogenization. For the sterilization method after dilute preparation, the final dilute solution is usually prepared according to the nature of the raw materials and in a certain sequence, and the finished product is obtained after sterilization and filling.
Water is a key ingredient in the formulation of drops, especially eye drops and nose drops. At BOC Sciences, we treat the water using technologies such as ion exchange treatment, ultrafiltration and distillation to ensure that the water used in the formulation meets purity standards. This prevents any unnecessary interaction between the water and the active ingredient, thus ensuring the stability and efficacy of the final product.
Clarity and color: Make sure the solution is free of particles and discoloration.
pH and osmotic pressure: Ensure that the formula is physiologically compatible with the eye, nose or ear environment.
Sterility and contamination testing: Each lot is tested to ensure it is free from microbial contamination.
Bulk drug size and particle size distribution (for suspensions) : In suspense-based formulations, ensure that the particle size is within an acceptable range for uniform drug delivery.
In vitro release: The in vitro release of an API can reflect changes in prescription and process and may affect the degree of absorption of the drug. Under normal circumstances, the in vitro release method should simulate the actual clinical use scenario as much as possible, and take into account the plateau period. The development of in vitro release method should include the selection of the type and volume of the release medium, sampling time point and temperature.
Drop volume: The human eye has a limited capacity for eye drops, too high drop volume will cause drug waste, too low drop volume may affect the efficacy of the drug.
For generic drops, appropriate packaging materials should be selected according to the packaging materials used in the reference preparation and product characteristics. In principle, the selected inner packaging materials should not be lower than the packaging materials used in reference preparations in terms of product protection and functionality. At the same time, the compatibility of products and packaging materials should be investigated, and the sealing property of packaging materials should be studied.
For stability, the stability test should be designed according to the characteristics of packaging materials (such as semi-permeable packaging materials, etc.). During the stability investigation, in addition to the general quality research items, the particle size and particle size distribution of the raw material, settlement volume ratio, resuspension/redispersability, content uniformity, antibacterial agent content, antioxidant content, water loss rate, etc., should also be investigated. If necessary, the in vitro release of the API should be considered. Stability test samples should usually be placed upright and upside down (or flat) in two ways.
The production of drops requires highly specialized equipment, such as blowing/filling/sealing machines, to ensure that the formulation remains sterile throughout the manufacturing process.
Our facilities are equipped with OEE (overall equipment efficiency) software to monitor process performance and efficiency, minimize downtime and ensure optimal batch quality.
High performance liquid chromatograph and nano particle size meter are used for quality control and analysis of eye drops, high performance liquid chromatograph is used for drug content determination and stability study, and nano particle size meter is used to detect drug particle size to ensure the uniformity of the preparation.
Automatic detectors detect impurities, defects or anomalies in filled containers. These systems use cameras and sensors to scan for particles, discoloration or filling problems, ensuring that only high-quality products make it into the packaging.
Nano technology is used to modify the drug to achieve continuous and stable drug release, reduce the number of doses and extend the action time of the drug at the treatment site
The development of a successful drop formulation requires a well-structured process flow, from concept to final product. At BOC Sciences, we follow a meticulous development plan that includes:
Water purification: Water used in formulations undergoes rigorous purification processes, including ion exchange, ultrafiltration, and distillation, to meet pharmaceutical-grade standards.
Formulation: Active ingredients and excipients are precisely weighed and mixed in a specific sequence to ensure optimal solubility and stability. Suspension-based formulations undergo additional steps to ensure even particle distribution.
Filling and sealing: The formulation is transferred to sterile containers using high-precision filling equipment under aseptic conditions. The containers are then sealed to prevent contamination.
Inspection and packaging: The final products are inspected for sterility, clarity, and other critical quality attributes before being packaged and prepared for shipment. BOC Sciences provides corresponding drug production and packaging services for clinical trial research.
1. What is the process of determining the quality of drops by HPLC?
Sample preparation: Take an appropriate amount of drop sample, add mobile phase to dissolve and shake well.
Chromatographic condition setting: Set chromatographic column, mobile phase, flow rate, detection wavelength, column temperature, sample amount and other parameters. For example, YSC-TRIART C18 column was used with mobile phase A of 5 mmol·L-1 ammonium acetate (containing 1% triethylamine, pH 5.0 of ice acetic acid), mobile phase B of acetonitrile, gradient elution.
Sample injection and analysis: Accurately take the right amount of sample solution into the chromatograph, record the chromatogram.
Result analysis: According to the peak area or peak height in the chromatogram, quantitative analysis was performed to calculate the drug content or impurity concentration.
2. How can nanotechnology improve drug release and bioavailability of eye drops?
Micelles, nano-suspensions, polymer nanoparticles, nanoemulsions and liposomes can increase the retention time of drugs on the ocular surface and the penetration through the cornea, thereby improving the bioavailability of local drug delivery. The positively charged chitosan nanoparticles contain cyclosporine A, which binds to tissues such as the cornea, prolongs the retention time in the eye, and can release the drug smoothly. After 48 hours of administration, the drug concentration of eye drops on the surface of cornea, conjunctiva and other tissues still maintained a high level.