Hydrophilic polymers as release modifiers for primaquine phosphate: Effect of polymeric dispersion

Sant S

Description

ABSTRACT
Primaquine (PQ), a synthetic compound with potent antimalarial activity is characterized by low plasma half life, requiring frequent administration leading to several undesired side effects, patient incompliance. The objective of the present study was to design an extended release formulation incorporating PQ in hydrophillic matrix composed of HPMC,Sodium CMC, Sodium alginate. Effects of polymeric dispersions of ethyl cellulose (EC) and polyvinylpyrrolidone (PVP) was also studied. Tablets were prepared by wet granulation method. The results of angle of repose (<30) and compressiblity index (upto 15%) indicate good flow properties. Tablets were subjected to weight variation, hardness, friability and drug content tests. The swelling and drug release profile were investigated under dissolution condition. The result showed that the swelling index & release retarding capacity follows HPMC>Sodium CMC>Sodium alginate, which was further sustained by polymeric dispersions of EC and PVP. The kinetics of drugs showed extended release of up to 20 hrs (F3) following non fickian diffusion (0.45RESUMEN
La primaquina (PQ), un compuesto sintético con actividad antimalaria fuerte, se caracteriza por tener una vida media de plasma baja, lo que requiere una administración frecuente y provoca varios efectos colaterales no deseados, con inconformidad del paciente. El objetivo del estudio actual fue diseñar una formulación de liberación prolongada que incorpora PQ en una matriz hidrofílica compuesta de HPMC, CMC de sodio y alginato de sodio. Se estudiaron también los efectos de las dispersiones poliméricas de etilcelulosa (EC) y polivinilpirrolidona (PVP). Los comprimidos se prepararon según el método de granulación húmeda. Los resultados de la respuesta de ángulo (<30) y el índice de compresibilidad (hasta el 15%) mostraron propiedades de flujo buenas. Los comprimidos se sometieron a pruebas de variación de peso, dureza, friabilidad y contenido de fármaco. La hinchazón y el perfil de liberación del fármaco se investigaron bajo condiciones de disolución. Los resultados mostraron que el índice de inflamación y la capacidad retardada de liberación son mayores con HPMC que con CMC de sodio, y que estos a su vez son mayores que con alginato de sodio, los cuales fueron más sostenidos por dispersiones poliméricas de EC y PVC. La cinética de los fármacos mostró una liberación prolongada de hasta 20 horas (F3) siguiendo una difusión no de Fick (0,45

Sujets

• Primaquine
• Alginic acid
• Fick's laws of diffusion

Informations

• Publié par: erevistas
• Publié le: 01 janvier 2011
• Nombre de lectures: 24
• Langue: English

Extrait

REVISTA CIENTÍFICA
Ars Pharmaceutica
Ars Pharm. 2011; 52(3)
FACULTAD DE FARMACIA. UNIVERSIDAD DE GRANADA. ESPAÑA
Editorial»
Martínez-Martínez F, Faus MJ, Ruiz-López MD.
Originales
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calcium and ezetimibe in multicomponent dosage form
Rajasekaran A, Sasikumar R, Dharuman J.
Hydrophilic polymers as release modifers for primaquine phosphate: Effect of »
polymeric dispersion
Sant S, Swati S, Awadhesh K, Sajid MA, Pattnaik GD, Tahir MA, Farheen S.
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Utilización terapéutica de los anticuerpos monoclonales»
García Ramos SE, García Poza P, Ramos Díaz F. Ars Pharmaceutica
Hydrophilic polymers as release modifers for
primaquine phosphate: Effect of polymeric dispersion
1 1 1 1 1 1 2Sant S , Swati S , Awadhesh K , Sajid MA , Pattnaik GD , Tahir MA , Farheen S .
1. Department of pharmaceutics, National Institute for Pharmaceutical Education and Research. 2. Azad Institute for Pharmacy
and Research.
Original Paper ABSTRACT
Artículo Original
Primaquine (PQ), a synthetic compound with potent antimalarial activity is characterized by
low plasma half life, requiring frequent administration leading to several undesired side effects,
Correspondence:
patient incompliance. The objective of the present study was to design an extended release
Md. Tahir Ansari
formulation incorporating PQ in hydrophillic matrix composed of HPMC,Sodium CMC, Sodium Department of pharmaceutics, National
institute for pharmaceutical education alginate. Effects of polymeric dispersions of ethyl cellulose (EC) and polyvinylpyrrolidone (PVP)
and research, Raebareli, Uttar pradesh,
was also studied. Tablets were prepared by wet granulation method. The results of angle of repose
India, 229010
(<30) and compressiblity index (upto 15%) indicate good fow properties. Tablets were subjected e-mail:[e-mail]
to weight variation, hardness, friability and drug content tests. The swelling and drug release
Received: 12.05.2010
profle were investigated under dissolution condition. The result showed that the swelling index Accepted: 25.05.2011
& release retarding capacity follows HPMC>Sodium CMC>Sodium alginate, which was further
sustained by polymeric dispersions of EC and PVP. The kinetics of drugs showed extended release
of up to 20 hrs (F3) following non fckian diffusion (0.45<n<0.89).
KEY WORDS: Primaquine phosphate, Extended release tablets, Hydroxypropylmethylcllulose,
Sodium CMC, Sodium alginate, Fickian
RESUMEN
La primaquina (PQ), un compuesto sintético con actividad antimalaria fuerte, se caracteriza por
tener una vida media de plasma baja, lo que requiere una administración frecuente y provoca varios
efectos colaterales no deseados, con inconformidad del paciente. El objetivo del estudio actual fue
diseñar una formulación de liberación prolongada que incorpora PQ en una matriz hidrofílica
compuesta de HPMC, CMC de sodio y alginato de sodio. Se estudiaron también los efectos de
las dispersiones poliméricas de etilcelulosa (EC) y polivinilpirrolidona (PVP). Los comprimidos
se prepararon según el método de granulación húmeda. Los resultados de la respuesta de ángulo
(<30) y el índice de compresibilidad (hasta el 15%) mostraron propiedades de fujo buenas. Los
comprimidos se sometieron a pruebas de variación de peso, dureza, friabilidad y contenido de
fármaco. La hinchazón y el perfl de liberación del fármaco se investigaron bajo condiciones de
disolución. Los resultados mostraron que el índice de infamación y la capacidad retardada de
liberación son mayores con HPMC que con CMC de sodio, y que estos a su vez son mayores que
con alginato de sodio, los cuales fueron más sostenidos por dispersiones poliméricas de EC y PVC.
La cinética de los fármacos mostró una liberación prolongada de hasta 20 horas (F3) siguiendo una
difusión no de Fick (0,45<n<0,89).
PALABRAS CLAVE: Fosfato de primaquina, Comprimidos de liberación prolongada,
Hidroxipropilmetilcelulosa, CMC de sodio, Alginato de sodio, Fickian.
Ars Pharm. 2011; 52(3): 19-25. 19Tahir MA, Sant S, Swati S, Awadhesh K, Sajid MA, Pattnaik GD, Farheen T, Saquib,Nadeem.
1/2 INTRODUCTION Q=(2ADC t) (1)
s
Primaquine phosphate, 8-[(4-amino-1-methyl butyl)
However, diffusion is generally not the only mechanism
amino]-6-metoxyquinoline phosphate, a synthetic
controlling the release. It has been reported that in aqueous
compound with potent antimalarial activity is considered
medium the polymer undergoes relaxation process resulting
to be a prominent medicine against resurgence and is also
in slow erosion of the hydrated polymer envisaging that
prescribed for terminal prophylaxis. It shows a broad
both the mechanism may work simultaneously contributing
spectrum activity against various stages of parasite,
13to the overall release rate Hydroxy propyl methyl
particularly asexual hepatic stages and latent tissue forms.
cellulose (HPMC) is the dominant hydrophilic vehicle
It is removed rapidly from blood. Excretion metabolism,
used for the preparation of oral controlled drug delivery
or tissue localization account for rapid elimination of
14systems The transport phenomena involved in the drug
1primaquine from the plasma . PQ is also characterized by
release from hydrophilic matrices are complex because the
2,3low plasma half-lives of 4-5 hrs , which require frequent
microstructure and macrostructure of HPMC exposed to
4administration and amplify its adverse effects . The
water is strongly time dependent. When it comes in contact
clinical use of primaquine for long period and repeated
with the gastrointestinal fuid, HPMC swells, gels, and
oral dosing can cause nausea, abdominal pain and
fnally dissolves slowly. The gel becomes a viscous layer
oxidant haemolysis with methemoglobinemia, anemia,
acting as a protective barrier to both the infux of water and
haemoglobinurea and is contraindicated in patients with
the effux of the drug in solution. Numerous studies have
different variants of glucose-6-phosphate dehydrogenase
been reported in literature investigating the HPMC matrices
5defciency . Moreover it may cause poor patient compliance
15,16to control the release of a variety of drugs . Sodium
leading to sub therapeutic primaquine concentration in
alginate have also been reported as release retarding agent
6plasma, promoting drug resistance . In order to improve
as hydration of an alginate matrix leads to a formation
the therapeutic effcacy of the drug and diminish its
17of gelatinous layer which acts act as a diffusion barrier .
toxicity, various approaches have been examined such
Sodium carboxy methyl cellulose (Sodium CMC) have also
7 8as nanoparticulate system , albumin carrier protiens ,
been explored as release modifers as it characterizes the
9 10nanoemulsions transdermal patches . Some researchers
18properties of hydrophilic polymers . Efforts were made
have proposed high dose over short administration
to gain optimum zero order release, hence present study
periods but PQ at high doses may affect gene expression
investigates the feasibility of incorporating polymeric
in liver and produce undesirable outcomes if administered
solution of ethyl cellulose (EC) and polyvinyl pyrrolidone
11over long time periods . Recently many controlled release
(PVP) into primaquine controlled release matrix system
formulation based on matrix system have been developed.
and to carry out In vitro investigation.
These delivery systems are characterized by controlled
release of the drug thereby reducing frequency of dosing
MATERIALS AND METHODS& hence decreasing fuctuation of plasma levels to obtain
Primaquine phosphate was supplied as gift sample from better therapeutic effects with reduced toxicity.
central drug research institute (Lucknow, India). HPMC,
Hydrophilic matrices are commonly used as oral drug Polyvinyl pyrrolidone (PVP) K90 was procured from
delivery systems and being increasingly investigated for Himedia (Mumbai,India). Ethyl cellulose was procured
development of controlled release drug delivery system from (Merck, India). All other ingredients used throughout
owing to compatibility, availability and economy. The the study were of IP grade and were used as received.
release properties of matrix system may be dependent
Preparation of sustained release matrix tablets:upon the solubility of the drug in the polymer matrix
Matrix tablets were prepared b