CB6960 Benzylpenicillin Diethylaminoethyl Ester Hydroiodide

Benzylpenicillin Diethylaminoethyl Ester Hydroiodide Description

Benzylpenicillin Diethylaminoethyl Ester Hydroiodide appears as a white to off‐white crystalline powder with negligible odour. Its high water solubility (>50 mg/mL at 25°C) results from the hydrophilic quaternary ammonium iodide moiety. It is only slightly soluble in ethanol and insoluble in nonpolar solvents. The compound decomposes at 198–202°C as a consequence of thermal instability induced by the iodide counterion. It must be protected from light to prevent photolytic degradation exceeding 15% within 24 hours (iodide‐mediated). Refrigerated storage at 2–8°C under an inert atmosphere is required to minimise acid‐catalysed β‐lactam ring hydrolysis and oxidative decomposition. Under these conditions, solid‐state stability is maintained for over 24 months.

As a prodrug, it is rapidly hydrolysed by esterases (>85% conversion) to release active benzylpenicillin, thereby yielding a 5–8‐fold increase in oral bioavailability relative to natural penicillin. This enhanced bioavailability is due to improved lipid solubility imparted by the diethylaminoethyl ester. Peak plasma concentrations are achieved within 1.5–2 hours post‐administration. The antibacterial spectrum is identical to that of benzylpenicillin G, targeting Gram‐positive bacteria while retaining sensitivity to β‐lactamases. HPLC purity is ≥98% with ≤1.0% moisture and ≤10 ppm heavy metals, where benzylpenicillin degradation products constitute the primary impurity (<1.5%).

Benzylpenicillin Diethylaminoethyl Ester Hydroiodide Applications

This prodrug derivative is used primarily for the oral treatment of penicillin‐sensitive Gram‐positive infections (for example, streptococcal pharyngitis, erysipelas, and uncomplicated bacteremia). It addresses the limitation inherent in natural penicillin which is only available for injection. The bioavailability of 60–70% permits rapid hydrolysis to active benzylpenicillin in the gastrointestinal tract, thereby producing serum concentrations comparable to those obtained via intramuscular injection within 2 hours. This pharmacokinetic profile benefits paediatric as well as geriatric patients who experience swallowing difficulties or a dislike of needles, and it is applicable in settings with limited resources where refrigeration (2–8°C) is available but where the administration of sterile injections is impractical.

The compound is additionally employed as a bridging therapy, permitting early transition from intravenous to oral penicillin during hospitalisation for conditions such as septicaemia, thereby reducing inpatient stays by 2–3 days. Its cost‐effectiveness in comparison with newer β‐lactams increases its accessibility within rural healthcare systems. However, clinical use is restricted to infections caused by non‐β‐lactamase‐producing pathogens, excluding most strains of Staphylococcus and Gram‐negative bacteria. Stability constraints necessitate light‐protected packaging and a cold chain during logistics, and drug interactions with antacids (due to pH‐dependent degradation) and probenecid (which competes for renal excretion) require careful management.

Benzylpenicillin Diethylaminoethyl Ester Hydroiodide Packaging

Our products are packaged in customised cartons of various sizes according to the material dimensions. Smaller items are securely packed in PP boxes, while larger items are placed in customised wooden crates. We strictly adhere to packaging customisation and utilise appropriate cushioning materials to ensure optimal protection during transport.

Packaging: Carton, Wooden Box, or Customised.

Kindly review the packaging details provided for your reference.

Manufacturing Process

1.       Testing Method

(1)    Chemical Composition Analysis – Techniques such as GDMS or XRF are applied to verify compliance with purity requirements.

(2)    Mechanical Properties Testing – Tensile strength, yield strength and elongation tests are performed to assess material performance.

(3)    Dimensional Inspection – Thickness, width and length are measured to confirm adherence to specified tolerances.

(4)    Surface Quality Inspection – Visual and ultrasonic examinations are conducted to detect defects such as scratches, cracks or inclusions.

(5)    Hardness Testing – Material hardness is determined to confirm uniformity and mechanical reliability.

Please refer to the SAM testing procedures for detailed information.

Benzylpenicillin Diethylaminoethyl Ester Hydroiodide FAQs

Q1. When is this penicillin prodrug typically prescribed?

It is prescribed primarily for the oral treatment of penicillin‐sensitive streptococcal infections (for example, strep throat and skin infections such as erysipelas) or as follow‐up therapy after initial intravenous antibiotic treatment for bacteremia. It is selected in instances where injections are impractical, for example with paediatric patients, elderly patients who have difficulties swallowing, or in remote clinics that lack sterile facilities.

Q2. Why must it be stored refrigerated?

The quaternary ammonium structure of the prodrug degrades under exposure to light and heat due to photolysis and β‐lactam hydrolysis. Storage at temperatures exceeding 8°C for more than 48 hours may reduce potency by 30–50%. Amber vials and blister packs are used to mitigate light exposure.

Q3. Can it replace all penicillin injections?

No. Its antibacterial spectrum excludes penicillin‐resistant bacteria (for example, β‐lactamase‐producing Staphylococcus aureus). Intravenous penicillin remains necessary for severe sepsis or meningitis. This prodrug functions as a bridging therapy to reduce the duration of hospitalisation.

Related Information

1.       Common Preparation Methods

The preparation begins by reacting benzylpenicillin potassium salt with diethylaminoethanol (1.2 molar equivalents) in anhydrous dimethylformamide (DMF) under a nitrogen atmosphere at -15°C to prevent β‐lactam degradation. This esterification uses N, N'-dicyclohexylcarbodiimide (DCC) as a coupling agent (0.95 eq) with catalytic 4-dimethylaminopyridine (DMAP, 0.1 eq). Strict moisture control (<0.05% water content) is maintained to avoid hydrolysis side reactions. After 8 hours of agitation, the intermediate benzylpenicillin diethylaminoethyl ester is isolated by precipitation into ice‐cold diethyl ether, yielding a white solid with a crude purity of approximately 85%.

Subsequent quaternisation involves dissolving this ester in acetone (5 vol) with methyl iodide (1.5 eq) at 20°C for 6 hours, forming the crystalline iodide salt. Reaction progress is monitored by TLC (silica gel, chloroform/methanol/ammonia 8:2:0.1 v/v). The crude product is then purified using cold ethanol recrystallisation (95% v/v, -20°C) to remove residual DCC byproducts, thereby achieving pharmaceutical‐grade purity (>98.5% HPLC). Final lyophilisation is performed from a tert‐butanol/water mixture (3:1) at -40°C to obtain a non‐hygroscopic powder, with strict light protection maintained throughout due to the risk of photodegradation.

Process scale‐up considerations include solvent recovery through DMF distillation under reduced pressure and controlling iodide residuals (<50 ppm) in accordance with ICH Q3D guidelines. The typical batch yield is 68–72% based on benzylpenicillin potassium salt.