Critical Factors Involved in the Determination of the Optimal
Concentration of Ophthalmic Anti-infective Compounded Drugs
Publication History:
Received: July 10, 2016
Accepted: December 26, 2016
Published: December 28, 2016
Keywords:
Ophthalmic, Drug, Cyclodextrins, Macromolecules,
Commentary Open Access
Introduction
Physiopathology characteristics of the eye make generally the
treatment of the ocular surface illnesses diicult. In addition to the
etiology, many times there is not any ocular commercial treatment
available due to economical or stability issues. In this cases
compounded drug are the alternative [1,2].
In ophthalmic pharmaceutical compounding, it is common to use
parenteral formulations for the preparation of ophthalmic drugs by
dissolution or dilution in eye compatible bufers. However, parenteral
drugs are not designed for or adapted to ocular administration, so
they can cause no desirable efects in the eye. On the other hand, we
barely have ocular toxicity and dose-respond studies of these drugs.
herefore, the concentrations utilised are chosen based on previous
results and clinical experience gathered over the years [3].
Moreover, the poor adaptation to the route and the tendency of
using simple formulations produce low eiciency systems, since
they have a low permanence inthe surface eye owing to the efective
precorneal clearance mechanisms [4]. In order to achieve therapeutic
concentrations, ophthalmologists prescribe eye dropswith high doses
of drugs, using very frequent instillations for extended periods of time.
his may cause great discomfort among patients that oten results in a
reduction in treatment adherence with the necessity of hospitalization
in order to obtain correct compliance and recovery [5].
he manifestation of ocular toxic efects is quite common and
can be caused by commercial medicines as well as by compounded
drugs. his can occasionally imply the interruption of the treatment.
here are tons of pharmacological groups of drugs for ocular route
with well-known potential toxicity, like NSAIDs or prostaglandin
analogues for glaucoma [6]. hese medicines, despite having gone
through a strict control by the regulatory agencies, have sometimes
signiicant toxicities. Another therapeutic group with well-known
ocular toxicity are the compounded drugs named as reinforced eye
drops of antibiotics. hese eye drops are used in the treatment of
complex bacterial keratitis in which it is necessary topic antibiotics
no commercially available or high concentrations of antibiotics which
treble the commercial concentrations [7].
It is diicult to achieve efective concentrations of drugs on the
ocular surface for long periods due tostrong precorneal clearance.
Diferent technologies have been tested to increase ocular retention
time, standing out the ones based onthe use of mucoadhesive
polymers, smart hydrogels and nanotechnology [8]. Bioadhesive
polymers increases the eye surface residence time by means unspeciic
or speciic interactions with the ocular mucosae prolong the residence
time [9]. In situ stimulus hydrogelsare utilised due to their ability of
modifying their consistence and structure when they are exposed to
external stimulus [9]. hese formulations gelled in the eye surface
*
Corresponding Author: Prof. Francisco Javier Otero Espinar, Pharmacy and
Pharmaceutical Technology Department, Faculty of Pharmacy, University of
Santiago de Compostela (USC), Spain, E-mail: francisco.otero@usc.es
Citation: Fernández-Ferreiro A, González-Barcia M, Gil-Martínez M, Blanco-
Méndez J, Luaces-Rodriguez A, et al. (2016) Critical Factors Involved in
the Determination of the Optimal Concentration of Ophthalmic Anti-infective
Compounded Drugs. Int J Clin Pharmacol Pharmacother 1: 122. doi: https://doi.
org/10.15344/2016/2456-3501/122
Copyright: © 2016 Fernández-Ferreiro et al. This is an open-access article
distributed under the terms of the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided
the original author and source are credited.
International Journal of
Clinical Pharmacology & Pharmacotherapy
Anxo Fernández-Ferreiro
1,3,4*
, Miguel González-Barcia
3,4
, Gil-Martínez M
5,6
, Blanco-Méndez J
1,2
, Luaces-Rodriguez A
1
,
Victoria Díaz Tome
1
, Lamas MJ
3,4
and Otero-Espinar FJ
1,2
1
Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), Spain
2
Instituto de Farmacia Industrial, Universidad de Santiago de Compostela (USC), Santiago de Compostela, España
3
Servicio de Farmacia. Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Santiago de Compostela, España
4
Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII), Spain
5
Servicio Otalmología. Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Santiago de Compostela, España
6
Instituto Otalmológico Gomez Ulla. Santiago de Compostela, España
Int J Clin Pharmacol Pharmacother IJCPP, an open access journal
ISSN: 2456-3501 Volume 1. 2016. 122
Fernández-Ferreiro et al., Int J Clin Pharmacol Pharmacother 2016, 1: 122
https://doi.org/10.15344/2016/2456-3501/122
by efect of a speciic stimulus forming a hydrogel ilm that releases
the drug [10]. he ocular surface provides properties (i.e. tear ion
concentration, pH or temperature) which facilitate the gelling of some
stimuli-responsive polymers that otherwise are in sol forms which can
easily be administered into the eye [8,11,12]. Finally the nanocarriers
can enhance the bioavailability of ophthalmic formulations by
means the improvement of the drug release properties, the surface
permanence and the drug penetration into the eye tissues.
On the other hand, poor aqueous solubility of some drugs
complicates their ocular administration. Hence, a challenge in the
ocular formulation is to achieve the incorporation olipophilic drugs
in ocular systems for pathologies with not many or none available
commercial alternatives. In order to reach that, it is indispensable
to increase solubility in water [13]. Cyclodextrins technology,
nanosuspensiones, polymeric micelles or the use of cosolvents or
hydrophilic polymers are useful pharmaceutical tools that aid in the
formulation of poorly aqueous soluble drugs [14].
he mentioned factors are just some of the ones thatmust be
assessed when designing a new ophthalmic formulation. For instance,
it is also necessary to determine optimal concentration of an anti-
infective when designing a new formulation for ocular infections.
Minimum Inhibitory Concentration in Ocular Opical
Formulations
Drug concentrations used in the current treatment of ocular
infections that afect anterior chamber are in revision. Eiciency of