Gel Formulations

Several prototype gel formulations are given in Table 9 to illustrate general compositional requirements and manufacturing methods. The design of specific systems tailored to meet predetermined, demanding performance criteria, particularly with respect to bioavailability, generally requires modification of published formulations or a totally original approach. 

Fig. 8 Comparison of time-release profiles from three different preparations of betaxolol (—) drug solution representing marketed product (--------) supension formulation (-----------) gel formulation.

Soaps, lotions, creams, washes, and gels are available in concentrations of 1% to 10%. The 10% concentration is not significantly more effective but may be more irritating. Gel formulations are usually most potent, whereas lotions, creams, and soaps have weaker potency. Alcohol-based gel preparations generally cause more dryness and irritation. 

Adapalene (Differin) is a third-generation retinoid with comedolytic, kera-tolytic, and antiinflammatory activity, ft is available as 0.1% gel, cream, alcoholic solution, and pledgets. A 0.3% gel formulation is also available. 

It is available in 20% cream and 15% gel formulations, which are usually applied twice daily on clean, dry skin. 

Comparative studies on the bioavailability of three different tretinoin gel formulations showed that the dimensions of the sampling area may play a critical role in determining the extent of dermal drug uptake [33, 34], If, by lateral spreading, a substance is distributed over an area sufficiently larger than the sampling area, significant proportions of compound will not be recovered and hence permeability will be underestimated. 

Leitner VM, Guggi D, Bernkop-Schnurch A (2004) Thiomers in noninvasive polypeptide delivery in vitro and in vivo characterization of a polycarbophil-cysteine/glutathione gel formulation for human growth hormone. J Pharm Sci 93 1682-1691. 

DCE gel formulations displayed minimal irritation in two separate in vivo rabbit studies. 

Conventional vaginal delivery systems include tablets, foams gels, suspensions, and pessaries. Mucoadhesive gel formulations based on polycarbophil have been reported to remain 3 to 4 days at the vaginal tissue, providing an excellent vehicle for the delivery of progesterone and nonoxynol-9 [66]. 

C. This could be attributed to the possible cross-linkages formed between the two polymers which thus restricted the movement of the drug molecules within the gel. The release of propranolol hydrochloride from the emulsion base, formulation D, was relatively low compared with all the hydrophilic polymeric gel formulations. This suggests that, for a water-soluble drug such as propranolol hydrochloride, polymeric-gel-based formulations are clearly the better vehicles for developing such dosage forms. 

Adverse local effects of the water-based gel formulation (MetroGel) include dryness, burning, and stinging. Less drying formulations may be better tolerated (MetroCream, MetroLotion, and Noritate cream). Caution should be exercised when applying metronidazole near the eyes to avoid excessive tearing. 

A topical 3% gel formulation of the nonsteroidal anti-inflammatory drug diclofenac (Solaraze) has shown moderate effectiveness in the treatment of actinic keratoses. The mechanism of action is unknown. As with other NSAIDs, anaphylactoid reactions may occur with diclofenac, and it should be given with caution to patients with known aspirin hypersensitivity (see Chapter 36). 

Islam MT, Rodriguez-Hornedo N, Ciotti S, Ackermann C. Fourier transform infrared spectroscopy for the analysis of neutralizer-carbomer and surfactant-carbomer interactions in aqueous, hydroalcoholic, and anhydrous gel formulations. AAPS J 2004 6(4) arti-... 

Silica precursors, tetraethoxysilane and tetramethoxysilane (TEOS and TMOS) are able to solvate some organic polymers. This enables the silica precursor to polymerize in the environment of an organic polymer solution. The number of polymers that form solutions with sol-gel formulations is, however, limited. Some initially soluble polymers tend to precipitate during gelation when a change in solvent composition leads to phase separation. 

Perry CM, Noble S. 1998. Saquinavir soft-gel formulation A Review of its use in patients with HIV infection. Drugs. 55 461-486. 

Fatty acid esters would be predicted to have little irritation or toxic effects. Ex vivo permeability studies conducted in porcine buccal mucosa showed significant permeation enhancement of an enkephalin from liquid crystalline phases of glycerine monooleate [32]. These were reported to enhance peptide absorption by a cotransport mechanism. Diethylene glycol monoethyl ether was reported to enhance the permeation of essential oil components of Salvia desoleana through porcine buccal mucosa from a topical microemulsion gel formulation [33]. Some sucrose fatty acid esters, namely, sucrose laurate, sucrose oleate, sucrose palmitate, and sucrose stearate, were investigated on the permeation of lidocaine hydrochloride [34], with 1.5% w/v sucrose laurate showing a 22-fold increase in the enhancement ratio. 

Messy semisolid gel formulations make administration difficult... 

A gelly microemulsion loaded with a phenyl phosphate derivative of zidovudine has been developed to prevent the HIV transmission [24]. This new drug also presents a spermicidal activity. The gel formulation is characterized by low cytotoxicity towards human vaginal,... 

Other vaginal gels with virucidal properties or capable of interfering with sexually transmitted diseases (in particular with HIV virus) have been reported [25], In particular, gel formulations based on a naphthalene sulfonate polymer named PRO 2000 and dextrin sulfate have been developed as topical microbicides to protect against HIV and other sexually transmitted pathogens. 

Sulfated polysaccharides are very poorly absorbed following oral administration, and efficacy upon parenteral administration has not been demonstrated. Their greatest potential may well reside in their topical application, i.e., as a gel formulation in the prevention of sexual HIV, and HSV, transmission. 

---