Liquid formulations

The bacterial culture converts a portion of the supplied nutrient into vegetative cells, spores, crystalline protein toxin, soluble toxins, exoenzymes, and metabolic excretion products by the time of complete sporulation of the population. Although synchronous growth is not necessary, nearly simultaneous sporulation of the entire population is desired in order to obtain a uniform product. Depending on the manner of recovery of active material for the product, it will contain the insolubles including bacterial spores, crystals, cellular debris, and residual medium ingredients plus any soluble materials which may be carried with the fluid constituents. Diluents, vehicles, stickers, and chemical protectants, as the individual formulation procedure may dictate, are then added to the harvested fermentation products. The materials are used experimentally and commercially as dusts, wettable powders, and sprayable liquid formulations. Thus, a... 

The DATs present in LAB will readily sulfonate to form dialkyltetralin-sulfonate or DATS. The foam and detergency performance properties of individual C DATS homologs are very similar to that of the corresponding C j LAS homologs [21]. Thus, even at a level of 10% DATS in the LAB, no decrease in foam or detergency performance is observed. In some liquid formulations, the presence of DATS can provide a beneficial hydrotropic effect to LAS [22]. Figure 8 illustrates that DATS are indeed surfactants, as evidenced by their surface tension vs. concentration plot. 

TABLE 5 LAS Homolog Formulation Characteristics in a Hand Dishwashing Liquid Formulation 24% LAS/6% AES/2% Amide/5 % SXS... 

The combination of LAS and ethoxylated alcohol has long been used in laundry powder and liquid formulations. A typical example of a phosphate version of such a formulation is shown below. The ethoxylate can be spray-dried with LAS in a complete formulation or it can be post-added to a spray-dried formulation containing LAS, phosphate, and other inorganics. 

Until the early 1980s, U.S. laundry liquid formulations contained combinations of LAS with AE (or even alkylphenol ethoxylate). Surfactant levels ranged from 20% to more than 40% active, and ratios ranged from high LAS/AE to low LAS/AE. Two examples of these laundry liquids are shown below. 

Typically the formulation may contain up to 60% active with builder salts and a water level of about 30-40% [52]. The weight ratio of LAS/AE may range from 1.5 1 up to 4 1. The combination of LAS and AE is especially effective for two reasons. First, LAS and AE interact strongly to form the lamellar phase liquid crystals. Second, both ingredients can be introduced into the liquid formulation as a 95 + % active liquid to control the amount of water going into the formulation. LAS can be introduced into the formulation as sulfonic acid and neutralized in situ. 

In contrast, for heavy-duty liquid formulations alkanesulfonates are an economically viable surfactant. An example for a typical formulation is given in Table 22. 

Thickeners and binders such as acacia, agar, starch, sodium alig-nate, gelatin, methyl cellulose, bentonite, and silica are used to improve product stability and enhance the convenience of the administration of a liquid formulation. Surface-active agents, colors, flavors and preservatives may also be used in the final formulation (Garcia et ah. Bioseparation Process Science, Blackwell Science, Malden, Mass., 1999, p. 374). 

In the cases where liquid formulations are applied, calibration is normally performed by collecting the output volume over a given time period. Generally a minimum of three such measurements should be taken in order to estimate output consistency. Where output is collected from multiple nozzles or outlets, each nozzle or outlet should be evaluated in order to ensure uniformity of output across all the nozzles or outlets. If the deviation from the manufacturer s recommended value is not within 5% (or the value specified in an appropriate SOP), the nozzle or outlet should be replaced. The use of a patternator allows the droplet distribution pattern of the nozzles or outlets to be measured accurately, and this check should be conducted annually. Having estimated the output of the equipment, the time required to treat a specific area with a known quantity of test item solution can be calculated. 

End-use formulations should be used as the test substance. If an active ingredient is marketed in two commercial formulations, then both should be used in the study, since there may be differences in residue levels and dissipation rates, e.g., a wettable powder versus a liquid formulation. The best solution would be plots located at the same site for a side-by-side comparison. This should only be necessary at one of the sites. However, each formulation should be represented in the study unless a strong case can be made for a worst-case scenario. 

Some antihistamines such as diphenhydramine, dimenhy-drinate, and meclizine are available without a prescription, making self-treatment convenient for patients. Antihistamines are available in a variety of dosage forms, including oral capsules, tablets and liquids. Liquid formulations are convenient for children or adults who are unable to swallow solid dosage forms. 

The controlled-release (CR) formulation is more slowly absorbed and longer acting than immediate-release tablets. Patients need to increase the total daily dose by 30%, as it is not as bioavailable as the immediate-release levodopa/carbidopa. The CR formulation has a delayed onset (45 to 60 minutes) compared to the standard formulation (15 to 30 minutes). Thus, patients may also need to take immediate-release tablets or even a liquid formulation when they want a quicker onset of effect, such as with the first morning dose.1,8,25... 

Patients with severe dyskinesias and off periods may achieve more constant blood concentrations (lower peak and higher trough concentrations) by taking a liquid formulation of levodopa with carbidopa. Each day patients make a 1 mg/mL levodopa... 

It was also established in laboratory work that this product could be readily formulated into dusts, wettable powder, or liquid formulations. Liquid formulations were more readily made with this than with the commercial benzene hexachloride, because of the higher concentration of the gamma isomer. 

USP Type III has been found acceptable in packaging some dry powders that are subsequently dissolved to make a buffered solution and for liquid formulations that prove to be insensitive to alkali. Type III glasses are usually not used for those products that are sterilized in their final container. Type II glass containers can be dry heat sterilized and filled under aseptic conditions. 

Oral Administration. Oral administration is the preferred route of administration. There is a general consensus among pediatricians and parents that children younger that 5 years of age have great difficulty with, or are unable to swallow, a solid oral dosage form. Manufacturers, therefore, have developed liquid formulations for many of the commonly used pediatric products. The liquid dosage form, however, is not free of problems. Liquid products are often unstable and have short expiration dates accurate measurement and administration of the prescribed dose is also a problem, especially in infants. 

Liquids and Suspensions. Most liquid formulations are not packaged in unit-dosage form. Therefore, before administration, the proper amount of medication to be taken for each dose must be measured. This additional requirement may compound any difficulties a patient may have in following a prescribed schedule. Patients suffering from visual impairment, arthritis, or tremors associated with neurological disorders are particularly likely to become frustrated with this type of formulation. Visual impairments make it difficult, if not impossible, for many elderly patients to measure the prescribed amounts of medication accurately. Impaired dexterity, owing to tremors or arthritis, may have effects on a patient s ability to hold both a spoon and a bottle at the same time while pouring out the desired amount of liquid. 

Klyashchitsky, B. A., Owen, A. J., Nebulizer-compatible liquid formulations for aerosol pulmonary delivery of hydrophobic drugs glucocorticoids and cyclosporine,... 

A simple, specific, and accurate reversed-phase HPLC method for the assay of niclosamide and several anthelmintics in veterinary products was reported [73], The method afforded rapid and efficient separation, good resolution, and identification of the examined compounds, alone or combined. The method was used to quantify these drugs, alone or in combination, in tablet, powder, and liquid formulations. 

There is growing concern over the potential risks to human health and the environment arising from leather goods. Dye manufacturers and tanneries are concerned about effluent, air pollution, containers and packaging [56]. In the light of the relatively important contribution to leather dyeing of azo dyes that can yield hazardous arylamines on reduction, careful guidance on the selection of dyes for leather is essential, with emphasis on procurement from reliable sources and the utilisation of liquid formulations to minimise... 

Dermal LDso values suggest that, irrespective of strain, female rats are more sensitive than male rats when disulfoton is administered dermally. The dermal LDso for disulfoton was determined to be 15.9 and 3.6 mg/kg in male and female Wistar rats, respectively (Mihail 1978). In Sherman rats, the dermal LDso was determined to be 15 and 6 mg/kg in males and females, respectively (Gaines 1969). In male Sprague-Dawley rats, the dermal LDso was determined to be 20 mg/kg (DuBois 1957). A dermal LDso value of 0.285 mL/kg (187 mg/kg) was reported for rats given a liquid formulation... 

Proteins must be stable during processing, storage, and reconstitution (if lyo-philized). Although liquid formulation is preferred for protein biopharmaceuticals, it may not always be the most stable presentation. The biopharmaceutical protein may need to be lyophilized to maintain stability. Lyophilization involves the removal of water from a frozen substance by sublimation and water vaporization under vacuum.17 But in some cases, this process may itself cause protein instability. 

Source Data from Remmele, R.L., Jr., N.S. Nightlinger, S. Srinivasan, and W.R. Gombotz. 1998. Interleukin-1 receptor (IL-1R) liquid formulation development using differential scanning calorimetry. Pharm Res 15 200-208. 

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