Pilocarpine emulsion

Emulsions have been used for centuries for the oral administration of medical oils and vitamins and as dermatological vehicles. Recently, their application has been extended as drug carriers in the delivery and targeting of ophthalmic drags. An indomethacin emulsion has been reported to increase ocular bioavailability and efficacy compared to commercially available formulation in rabbits. 0.4% indomethacin emulsion showed 2.2 fold increase in the area under the anterior aqueous drag concentration/time curve compared to a 1% indomethacin suspension. The emulsion formulation also reduced ocular surface irritation caused by indomethacin Similar advantages have been shown for a pilocarpine emulsion which produced a prolonged therapeutic effect in comparison with pilocarpine hydrochloride eyedrops in man. It can be administered only twice a day, rather than four times daily for conventional formulation. 

Naveh, N., S. Muchtar, and S. Benita. 1994. Pilocarpine incorporated into a submicron emulsion vehicle causes an unexpectedly prolonged ocular hypotensive effect in rabbits. J Ocul Pharmacol 10 509. 

Zurowska-Pryczkowska, K., M. Sznitowska, and S. Janicki. 1999. Studies on the effect of pilocarpine incorporation into a submicron emulsion on the stability of the drug and the vehicle. Eur J Pharm Biopharm 47 255. 

Sznitowska, M., et al. 2001. In vivo evaluation of submicron emulsions with pilocarpine The effect of pH and chemical form of the drug. J Microencapsul 18 173. 

Sznitowska, M., et al. 2000. Increased partitioning of pilocarpine to the oily phase of submicron emulsion does not result in improved ocular bioavailability. Int J Pharm 202 161. 

Garty, N., and M. Lusky. 1994. Pilocarpine in submicron emulsion formulation for treatment of ocular hypertension A phase II clinical trial. Invest Ophthalmol Vis Sci 35 2175. 

Multiple emulsions have been used to deliver active agents with prolonged release in dermatological treatments. For example, O/W/O emulsions have been used to deliver pilocarpine hydrochloride as a myopic agent in eye infections [440]. Here the active agents was placed in the internal oil phase of the O/W/O emulsion to provide an appropriate rate of release. Similar approaches have been used in other treatments, using W/O/W emulsions [440]. 

New sustained technologies are also gaining much interest in ocular delivery, as in other routes. Liposomes as drug carriers have achieved enhanced ocular delivery of certain drugs, antibiotics, and peptides. Prolonged delivery of pilocarpine can be achieved with a polymeric dispersion or submicrometer emulsions [79]. 

Beilin, M., Bar-Ilan, A., and Amselem, S. (1995), Ocular retention time of submicron emulsion (SME) and the miotic response to pilocarpine delivered in SME. Investigative Ophthalmol. Vis. Sci., 36, S166. 

Garty, N, Lusky, M., Zalish, M., Rachmiel, R., Greenbaum, A., Desatnik, H., Neumann, R., Howes, J. F., and Melamed, S. (1994), Pilocarpine in submicron emulsion formulation for treatment of ocular hypertension A phase II clinical trial, Investigative Ophthalmol. Vis. Sci., 35,2175. 

Pilocarpine is a drug commonly used in glaucoma therapy to relieve intraocular pressure (lOP), which is a cause of great discomfort to the patient. Piloplex is a sustained-release product based on an emulsion system of pilocarpine bound to a polymeric carrier [87,88]. Piloplex was shown to prolong a reduction in lOP as compared to standard pilocarpine hydrochloride drops. This is attributed to its bioadhesive properties, which keep the drug in the precorneal area longer than do conventional ocular dosage forms. 

In this formnlation, pilocarpine is bound to a polymeric material and this complex makes up the internal, dispersed phase of the emulsion system, in vitro studies have indicated that the release time of 80% of the pilocarpine from this system is 6 h compared to 80% released in only 1 h from pilocarpine hydrochloride solntion thus, the prolonged therapeutic effect is apparently due to both an enhanced pnlse entry of drng and to a prolongation of drug release from the vehicle. 

Multiple emulsions have been used to deliver active agents with prolonged release in dermatological treatments. For example, O/W/O emulsions have been used to deliver pilocarpine hydrochloride as a myopic agent in eye infections... 

Contrary to instillation of standard eyedrops, unilateral application of emulsified pilocarpine induced a biphasic effect in (he contralateral eye, presumably due to systemic absorption. The authors concluded tha(, in spite of (his drawback, (he pilocarpine submicrometer emulsion might serve as a long acting antiglaucoma preparation, requiring a single daily instillation. In another... 

FIG. 16 Comparison of the miotic effect after ocular administration of a submi-crometer emulsion containing 1.2% (w/v) pilocarpine prodrug or aqueous solutions containing 0.5% (w/v) or 2.0% (w/v) pilocarpine HCl. (From Ref. 133 with permission from Elsevier Science.)... 

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