Evaluation of in vitro-in vivo correlation and anticonvulsive effect of carbamazepine after cogrinding with microcrystalline cellulose.

نویسندگان

  • Mohammad Barzegar-Jalali
  • Alireza Mohajjel Nayebi
  • Hadi Valizadeh
  • Jalal Hanaee
  • Azim Barzegar-Jalali
  • Khosro Adibkia
  • Mahdieh Anoush
  • Mohammad Sistanizad
چکیده

PURPOSE Carbamazepine is a poor water soluble drug and its bioavailability is limited by dissolution rate. Dissolution, serum concentration and anticonvulsive effect of the drug have been evaluated after cogrinding with microcrystalline cellulose. A cogrinding technique was used to increase the dissolution, serum concentrations and anticonvulsive effect of the drug. A novel deconvolution technique of in vitro in vivo correlation was evaluated. METHODS The drug coground with microcrystalline cellulose, the corresponding physical mixture, unground and ground drug powder were subjected to dissolution measurement. Coground and unground drug serum concentrations were investigated in rabbits. Also the anticonvulsive effects of the latter preparations were assessed in mice. For elucidation of observed in vitro and in vivo differences FT-IR spectroscopy, X-ray diffraction patterns and DSC thermograms of the preparations were studied. RESULTS The dissolution of the coground was the highest (percent dissolved in the first 20 minutes, %D20', was 97.5). The unground drug powder exhibited the lowest dissolution (%D20'=40). The difference was reflected in their corresponding area under the mean serum concentration curves between 0-16 hr (118.96 vs 54.17 microg x hr/ml) as well as protection abilities against strychnine and electrically induced seizures. The onset of tonic seizures induced by strychnine was increased between 40-140% in the case of the coground system depending on dose and time of carbamazepine administration. CONCLUSION Cogrinding was an effective technique in increasing carbamazepine dissolution due to reduced crystallinity as seen in X-ray pattern, enhanced wettability and decreased particle size, which in turn resulted in increased serum concentrations and its anticonvulsive effect. A novel simple deconvolusion technique not requiring intravenous data denoted as the double reciprocal area method was used to establish correlation between in vitro and in vivo parameters.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Anesthetic effects of lidocaine hydrochloride gel using low frequency ultrasound of 0.5 MHz.

PURPOSE Low-frequency ultrasound has a significant effect on the transdermal permeation of high molecular weight drugs. However, the rate of permeation in pulsed mode is quite low necessitating considerable time to apply the ultrasound. 0.5 MHz ultrasound, which is a relatively higher frequency in the low-frequency range, can be applied in high intensity in continuous mode. METHODS A transduc...

متن کامل

Evaluation of Carbamazepine (CBZ) Supersaturatable Self-Microemulsifying (S-SMEDDS) Formulation In-vitro and In-vivo

The supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) represents a new thermodynamically stable formulation approach wherein it is designed to contain a reduced amount of surfactant and a water-soluble polymer (precipitation inhibitor or supersaturated promoter) to prevent precipitation of the drug by generating and maintaining a supersaturated state in-vivo. The supersatur...

متن کامل

Evaluation of Carbamazepine (CBZ) Supersaturatable Self-Microemulsifying (S-SMEDDS) Formulation In-vitro and In-vivo

The supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) represents a new thermodynamically stable formulation approach wherein it is designed to contain a reduced amount of surfactant and a water-soluble polymer (precipitation inhibitor or supersaturated promoter) to prevent precipitation of the drug by generating and maintaining a supersaturated state in-vivo. The supersatur...

متن کامل

Role of Cogrinding in Enhancing the In vitro Dissolution Characteristics of Carvedilol

In the present study, an attempt was made to increase the in vitro dissolution rate of carvedilol (antihypertensive) by cogrinding technique using various carriers, namely lactose, corn starch, treated agar, microcrystalline cellulose. The coground mixtures were prepared using the above excipients in four drug-carrier ratios, viz., 1:1, 1:3, 1:4 and 1:9. The prepared coground mixtures were eval...

متن کامل

Formulation and Evaluation of Propranolol Hydrochloride-Loaded Carbopol-934P/Ethyl Cellulose Mucoadhesive Microspheres

The purpose of this research was to formulate and systemically evaluate in-vitro and in-vivo performances of mucoadhesive propranolol hydrochloride microspheres for its potential use in the treatment of hypertension, myocardial infraction and cardiac arrhythmias. Propranolol hydrochloride mucoadhesive microspheres, containing carbopol-934P as mucoadhesive polymer and ethyl cellulose as carrier ...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques

دوره 9 3  شماره 

صفحات  -

تاریخ انتشار 2006