Hydrophilic Ointment RQ-126

Hydrophilic Ointment RQ-126 is a preserved oil-in-water emulsion vehicle supplied as a white to off-white semisolid with a continuous aqueous phase and an internal petrolatum phase. The RQ-126 model designation identifies a fixed nonionic emulsifier matrix consisting of purified water, propylene glycol, cetostearyl alcohol, polysorbate 60, white petrolatum, methylparaben, and propylparaben; it contains no anionic surfactant. The pH of a 1:10 aqueous dispersion is 4.5–6.5 when measured according to USP <791> at 25 °C. Apparent viscosity at 25 °C falls within 450,000–650,000 mPa·s using a Brookfield Helipath T-bar spindle T-E at 2.5 rpm. The emulsion is manufactured by high-shear homogenisation at 3,000–4,500 rpm, filtered through a 200 µm inline screen, and cooled at 0.5–1.0 °C/min to 25 °C. RQ-126 is not a pharmacopoeial monograph vehicle but is released for nonsterile dermatological compounding under USP <795>; it is not sterile and is not intended for ophthalmic, parenteral, vaginal, or other sterile-route applications.

In dermatological compounding, RQ-126 functions as a water-washable vehicle for corticosteroids, sulphur, salicylic acid, coal tar solution, zinc oxide, and other nonsterile topical actives. The internal petrolatum fraction of 15–20% w/w forms an occlusive residual film after application, while the aqueous external phase permits removal with water. For levigation of zinc oxide or sulphur, a portion of RQ-126 is first combined with the powder at a 1:1 ratio by geometric dilution in a glass or porcelain mortar, followed by successive additions of the remaining vehicle. The practical upper powder loading is 30% w/w; beyond this limit, spreadability decreases and visible phase separation may occur within 72 h at 25 °C. The buffering capacity of the external phase is limited to approximately 0.02 mol/L; strongly acidic or basic additives can exhaust this capacity and shift the product outside its target pH range.

Which Formulation Variables Control Release and Viscosity in RQ-126?

Viscosity is governed primarily by the fatty alcohol–polysorbate 60 gel network rather than by the dispersed petrolatum phase alone. Oscillatory rheometry at 25 °C and 1 Hz gives a storage modulus G′ of 7,000–9,000 Pa and loss modulus G″ of 1,800–2,400 Pa for a reference batch. A 2 °C reduction in the emulsification hold temperature from 65 °C lowers G′ by 12–18%, while a 2 °C increase weakens the gel network and reduces yield stress from 320–380 Pa to 210–250 Pa. The cooling step is the dominant processing variable: batches cooled faster than 1.5 °C/min show a grainy appearance after 30 days at 40 °C and an increase in serum separation from 0.8% to 3.4% by visual index. Propylene glycol at 10–15% w/w depresses the aqueous freezing point and retains the preservative fraction in the water compartment; reduction of propylene glycol below 8% w/w increases preservative migration into the petrolatum phase and lowers the free aqueous preservative concentration below the target range.

For hydrocortisone 1% w/w, in vitro release through a polysulfone membrane in a vertical diffusion cell at 32 °C and 600 rpm reaches 68–74% in 6 h, compared with 38–42% for white petrolatum and 52–58% for a conventional anionic hydrophilic ointment under the same apparatus conditions described in USP <1724>. The higher flux is attributed to the aqueous continuous phase and propylene glycol, but the rank order may differ for lipophilic actives with log P above 4. Published data for RQ-126 with such actives are limited and should be experimentally confirmed before formulation finalisation.

On a 500 kg jacketed scraped-surface kettle with a rotor-stator homogeniser, the aqueous phase is heated to 70–75 °C and the oil phase to 68–72 °C. The oil phase is added to the aqueous phase over 8–12 min at 3,500 rpm. The homogeniser is stopped when the product temperature reaches 55–58 °C, and anchor agitation continues at 20–25 rpm during the controlled cooling ramp. In-process viscosity at 65 °C is 18,000–24,000 mPa·s before gel network formation; final viscosity is attained only after 24 h at 20–25 °C. Process hold times above 12 h at 55 °C can depress final viscosity by 20–30% and should be avoided because the fatty alcohol network requires a defined thermal history to mature. Across 45 production batches, coefficient of variation for final viscosity is 6.2% when cooling rate is maintained within 0.5–1.0 °C/min; outside this window, coefficient of variation increases to 14.8%.

Cooling-Rate Sensitivity and Preservative Partitioning

The preservative efficacy of RQ-126 depends on the free aqueous concentration of methylparaben and propylparaben, which partitions into the fatty alcohol gel network as it crystallises. At 25 °C, the measured free aqueous methylparaben concentration is 0.09–0.12% w/w at a total methylparaben loading of 0.18% w/w. This satisfies the acceptance criteria of USP <51> against Candida albicans ATCC 10231, Staphylococcus aureus ATCC 6538, and Pseudomonas aeruginosa ATCC 9027, with no less than 1.0 log reduction at 14 days and no increase from the initial count at 28 days. Cooling faster than 1.0 °C/min reduces gel network surface area and increases the free preservative fraction above the original equilibrium. Cooling slower than 0.3 °C/min permits excessive cetostearyl alcohol crystallisation, raising viscosity above 800,000 mPa·s and producing a product that is difficult to spread. Homogenisation at 3,000 rpm yields a droplet size D[4,3] of 5.8 µm, while 4,500 rpm yields D[4,3] of 2.5 µm; droplet size below 2.0 µm raises interfacial area and reduces free preservative concentration by approximately 15%.

Microbial limits are confirmed by USP <61> and USP <62>. The release specification permits total aerobic microbial count not more than 10² CFU/g and total combined yeasts and moulds not more than 10¹ CFU/g. Absence of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans is required in 1 g. RQ-126 is manufactured under controlled nonsterile conditions and has not been terminally sterilised; therefore it is not acceptable for application to sterile body cavities or to denuded skin where a sterile product is required. Terminal steam sterilisation is incompatible with RQ-126 because autoclaving causes emulsion inversion and irreversible oil-phase coalescence. If a sterile vehicle is required, an alternative product must be selected.

When RQ-126 Is Combined with Charged API Salts or Solvent Systems

Incorporation of lidocaine hydrochloride at 5% w/w reduces apparent viscosity at 25 °C by 8–12%. At 15% w/w, the emulsion may exhibit serum separation after 48 h at 25 °C because the added electrolyte increases the ionic strength of the external phase beyond 0.3 M. The threshold is lower for polyvalent salts such as aluminium chloride and zinc sulfate; for these materials, even 2% w/w can cause a visible aqueous phase to separate within 24 h. Published data for RQ-126 with specific polyvalent electrolytes beyond these model studies are limited, and compatibility testing under ICH Q1A(R2) accelerated conditions is required before compounding. The product should not be mixed with strong oxidising agents, including benzoyl peroxide at concentrations above 5% w/w, because the petrolatum and fatty alcohol components are susceptible to oxidative rancidity. The product should not be combined with strong alkalis if the resulting pH exceeds 7.5, because methylparaben degradation in forced alkaline conditions can exceed 5% after 14 days at 40 °C.

Because RQ-126 has an aqueous external phase, aqueous stock solutions may be incorporated up to 10% v/w of the final mass without unacceptable viscosity loss. Alcoholic solutions should be limited to 5% v/w because ethanol concentrations above this level reduce gel network viscosity and may cause droplet coalescence. The water activity of 0.82–0.88 at 25 °C is sufficiently low to limit the growth of many vegetative organisms but does not preclude microbial growth after contamination. Therefore any dilution with unpreserved solutions reduces the preservative reserve, and the compounded preparation should be assigned a beyond-use date no longer than 30 days under USP <795> unless a longer stability study supports otherwise.

The absence of anionic surfactant distinguishes RQ-126 from the compendial USP Hydrophilic Ointment. In a stainless steel compounding vessel, cationic active pharmaceutical ingredients such as benzethonium chloride and benzalkonium chloride show immediate precipitation when added to the anionic USP vehicle, whereas in RQ-126 the same actives remain homogeneously dispersed for at least 7 days at 25 °C. This compatibility difference is the primary formulation selection criterion for certain antiseptic and local anaesthetic applications. However, the nonionic network is less tolerant of high-shear post-processing than the anionic reference; extended homogenisation after gel formation can reduce final viscosity by 25% and should be avoided.

Storage in high-density polyethylene jars at 15–30 °C is specified. Brief excursions up to 40 °C for 24 h are acceptable, but freezing below -5 °C is prohibited because ice crystal formation in the external phase breaks the gel network and causes irreversible serum separation upon thawing. Do not use RQ-126 after visible separation, a colour change to yellow, or the development of a rancid odour. For moisture-sensitive actives, published data on chemical stability in RQ-126 are limited; accelerated stability studies under ICH Q1A(R2) with the specific active pharmaceutical ingredient are required before compounding.