DMSO and Lidocaine Solution – Gaylord Chemical

DMSO and Lidocaine Solution - Gaylord Chemical

Lidocaine is a local anesthetic that provides loss of sensory, motor and autonomic function. It does this by binding to sodium channels in the lining of the skin and reversing nerve endings without causing damage. It is usually given in mucosal, dermal, topical dosage forms. It can also be injected in close proximity to nervous tissue. (1,2)

Lidocaine is an amide-type local anesthetic. It is metabolized in the liver by microsomal P-450 enzymes n-Dealkylation and hydroxylation. When applied topically, lidocaine has a faster but less anesthetic effect. Topically applied lidocaine has a low anesthetic due to its poor percutaneous absorption. Although pastes, creams and ointments are considered safe methods of application, they are easily removed with wetness, movement, and contact. To overcome these disadvantages, a new formulation strategy was published by Omar et al. (2)

A bio-adhesive preparation with enhanced anesthetic effect was introduced. In this strategy, the vesicular system was fundamentally used as vehicles for topical, mucosal, dermal and transdermal drug delivery. The vesicular system has shown benefits that aid in improving the permeation of the drug. Transferosomes have proven to be a better topical drug delivery system. (2)

Transferosomes are made of ultra-flexible bilayer membranes, making them highly elastic and deformable. They can squeeze through the pores of the stratum corneum, which is one-tenth the size of the transferosome. Since transferosomes have a liquid character, they can be combined with a suitable vehicle, such as hydroxypropyl methyl cellulose (HPMC). This gelling agent maintains the vesicular structure and has gelling properties compatible with transferosomes. HPMC is also non-toxic, has favorable anti-inflammatory properties and can accommodate high levels of medication. Such a formulation was studied intensively by Omar et al. (2)

The main objective of the work was to study the incorporation of transferosomal lidocaine into the gel, its trapping efficiency, in vitro drug release, skin retention and its analgesic effect. This formulation was also combined with DMSO, which was used as a skin penetration enhancer. Transferosomes were prepared by the thin film hydration method:

Figure 1: Flow Chart Representation of the C Method Used My Omar et al. (2)

Transferosomes were collected after high-speed centrifugation and zeta potential and particle size were evaluated. To confirm that the transferosomes were loaded with lidocaine, the drug loading and entrapment efficiency of the transferosomes were calculated. The release profile of the transferosomes indicated that more than 80% of the drug content of the prepared vesicles was released after 6 h. The formulation led to a controlled release of lidocaine due to the transferosome reservoir effect. An eruptive effect or exponential phase was observed in the first 4 hours, after which the release slowed down or reached a plateau phase. The burst effect is explained by the property of a bilayer to lose surface-associated material or the inability of the transferosome to hold large amounts of lidocaine, which were immediately expelled from the vesicles in the first 4 hours. The kinetic profile of lidocaine released from the transferosome indicated that it followed a first order reaction model. (2)

Figure 2: Graphical representation of the burst effect discussed in the study (2)

The stratum corneum is a rate limiting barrier for transdermal permeation. It plays an important role in homeostasis and acts as a barrier to protect the body from the external environment. Although transferosomes can easily pass through the pores of the stratum corneum, this is still considered a rate limiting step. To overcome this, and to increase the amount of lidocaine available, DMSO was added to the formulation. DMSO showed a significant increase in the permeability profile of the transsomal lidocaine-containing gel. Transduction of lidocaine from transferosome with DMSO was 43.74 2.74%, compared to lidocaine from transferosome without DMSO and lidocaine solution was 19.81 1.99% and 22.45 2.85%, respectively. Although denatured transferosomes increased the amount of bioavailable lidocaine, the authors concluded that DMSO further increased the bioavailability. The amount of lidocaine retained in the skin was also significantly higher with DMSO (18.41%) than with lidocaine alone (5.45%). Additionally, in the presence of DMSO, lidocaine-transferosomes (6.98%) produced a high anesthetic effect. This tail flick was demonstrated using the Rat Tail Test.

The findings suggest that DMSO enhanced the transdermal penetration of lidocaine by improving drug partitioning between skin layers. (2)

References:

  1. Klaus D. et al; StatPearls Publications; 2020 January
  2. Omar et al; International Journal of Nanomedicine 2019:14 1551-1562

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