Mol2Net Statistically optimized binary ethosomal gel of Carvedilol: - PDF document

Mol2Net , 2015 , 1( Section A, B, C, etc. ), pages 1- x, type of paper, doi: xxx-xxxx 1 http://sciforum.net/conference/mol2net-1 SciForum Mol2Net “ Statistically optimized binary ethosomal gel of Carvedilol: allevialates hypertenstion in male Wistar albino rats” Thota Sunil Kumar 2 and Ananda Kumar Chettupalli *,1 2. Department of Pharmaceutics, University college of Pharmaceutical Sciences (UCPSc), Kakatiya university, Vidyaranyapuri, Hanamakonda, Warangal, Telangana 506009, India. sunithasunilthota@gmail.com, +91- 9849237235, +91- 9502020950. * Department of Pharmaceutics, School of Pharmacy, Anurag Group of Institution, Venkatapur, Medchal, Hyderabad-500088, Telangana, India.- anandpharmacy@cvsr.ac.in +91- 9849922424, +91- 6303132567. Received: / Accepted: / Published: Abstract: The current study entails novel advanced formulation approach binary ethosomal gel containing Carvedilol and evaluating the optimized formulation for hypertension. Carvedilol is an antihypertensive agent, which undergoes hepatic metabolism and shows poor bioavailability of just 20 %. Carvedilol binary ethosomal suspension was optimized using central composite design (CCD). In which quantities of lipid (A), ethanol (b), and propylene glycol (C) were selected independent variables; vesicle size (Y1), entrapment efficiency (Y2) and cumulative %drug release (Y3) were selected as dependent variables. The composition of optimum formulation was found as 2 % of lipid (Soya lecithin), 20 % of ethanol, and 10 % of propylene glycol. The optimized binary ethosomal suspension (OBE) had shown a vesicle size, poly dispersable index, ztapotential, cumulative % drug release, and %entrapment efficiency of 130±1.72nm, 0.230±0.03, -31±1.8MV, 97.89±3.7 %, and 99±2.96 % respectively. This was further evaluated and compared with liposomes. Scanning electron microscopy studies revealed that OBE was in spherical shape. The OBE was converted to hydrogel and evaluated for rheological properties. The OBE- Gel (OBE-G) attained mean transdermal flux of 0.0644±0.002 mg/cm 2 .h through rat skin. This formulation showed a substantial and constant decrease

in blood pressure, for up to 24 h. The OBE-G was found to be effective, with reduction in blood pressure by virtue of better permeation through rat skin. In conclusion, OBE-G accentuate the transdermal flux and the results obtained encouraged its use for hypertension treatment. Keywords: Carvedilol; Central composite design; hydrogel, hypertension. 1. Introduction Transdermal drug delivery offers benefits with a lipid bilayer. It can penetrate easily over other routes of administration, which through SC and increase the amount of drug includes avoidance of pre-systemic metabolism delivery effectively [5][6].Further, for improving and betterment of compliance. Unfortunately, the the consistency of the final dosage form, OBE formidable barrier characteristics of stratum was converted to hydro gel making it convenient corneum (SC) present a significant obstacle for for application on the skin surface of the patient. most drugs to be delivered through it. To Carvedilol is rapidly absorbed after oral surmount this barrier, new approaches of administration, however, it possesses low oral advanced vesicular carriers have been specially bioavailability (about 20%) and high lipophilicity designed for the efficient delivery of active (Log P = 4.1) attributed to its poor dissolution pharmaceutical ingredient (API) with different (biopharmaceutical classification system (BCS physicochemical properties across the skin. [1] class II) and extensive pre systemic metabolism [2]. [6][7]. The incorporation of the drug into lipid Ethosomal systems are lipid vesicular carriers carriers leads to enhancement of bioavailability. containing a high percentage of ethanol, probably Various formulation approaches like solid lipid this makes the vesicle membrane leaky, further nanoparticles (SLNs) and nasal microspheres leads to decrease in entrapment efficiency and have been employed to circumnavigate the stablity [3] [4]. Therefore, to enhance stability, hepatic route in order to increase carvedilol binary ethosomes have been developed. Which bioavailability [7]. comprised of ethanol and propylene glycol (PG)? Statistical designs help in optimization of Binary ethosomes have an intact spherical shape formulation under a given set of conditions and

Mol2Net , 2015 , 1( Section A, B, C, etc. ), 1- x, type of paper, doi: xxx-xxxx 3 pre-determined goals. Among the various effects. Thus, CCD was employed for optimizing designs available, the central composite design quality attributes of the prepared vesicles. [8] [9]. (CCD) is a popular form of response surface Thus, the scope of the present work was methodology (RSM) which has been extensively to evaluate the OBE-G of carvedilol developed employed in optimization and identifying the using a statistical approach like Central best formulation. This design is considered to be composite design. Furthermore, the work also efficient in estimating the influence of individual investigates the enhancement of therapeutic variables (main effects) and their interaction potential of OBE-G using ex-vivo permeation and pharmacodynamic studies. [10] [11]. 2. Results and Discussion Experimental design optimization and In the regression equation the sign and response surface approach value are the quantitative effect which represents the tendency and magnitude of the term’s Statistical analysis The results implied that this system was influence on the response. ANOVA for the colossally swayed by the amount of lipid, responses indicated that the quadratic regression ethanol, and PG which resulted in small vesicle model was significant and valid for each of the sizes, high % EE and high cumulative % drug responses Y1 (p<0.0001), Y2 (p<0.0001) and release of the prepared ethosomes. The Y3 (p<0.0001) and hence was appropriate to regression equations (4) – (6) were obtained using represent the observed data, respectively which are shown in Table 3.The observed R 2 values for DoE. Y1 =+328.21-34.45 A+302.50 B-87.68 C-143.50 AB-80.50 the dependent responses are 0.9890, 0.9887 and AC+16.00 BC+127.57 A²+136.05 B²+5.24 C² 0.9662. When the observed value of R 2 was at Y2 =+95.43+7.59 A-9.87 B+2.15 C+13.21 AB+4.10 AC- least 0.80, it implied a good correlation and was 4.88 BC-8.90 A²-8.02 B²+0.8494 C² found in all cases, indicating a good fit by the Y3 =+94.98+4.71 A-7.72 B+2.63 C +8.21 AB+2.95 AC- model (41). The R 2 values, for size (Y1) is 0.8025 BC-1.23 A²-4.21 B²-0.7502 C² 0.9790, % EE (Y2) is 0.9785 and Cumulative %

Mol2Net , 2015 , 1( Section A, B, C, etc. ), 1- x, type of paper, doi: xxx-xxxx 4 DR (Y3) is 0.9358 are high and advocated the release) were 130 nm, 99 %, and 99.98 % significance of the model. The R 2 Pre values, for respectively. size (Y1) are 0.9203, % EE (Y2) is 0.9318 and A new batch of ethosomal suspension Cumulative % DR (Y3) is 0.9025, given by the according to the optimal formulation was model, which indicated a correlation between formulated in order to confirm the predicted the predicted and observed values. Hence, the model,. The observed OBE had shown a vesicle response model of this system is highly suitable size, PDI, ZP, Cumulative % drug release and % for the selected responses. By using RSM the EE of 130±9.72nm, 0.230±0.03, -31±3.8Mv, independent variables and their interactions on 99.98±3.7 % and 99±2.08% respectively. A dependent responses were graphically comparison between the results indicated the represented by 3D surface plots. The effect of reliability of CCD in predicting a desirable the amount of lipid, the amount of ethanol and ethosomal formulation. the amount of PG on vesicle size, % EE and Solid-state characterization cumulative % DR are represented in Fig 1. Fourier transform infrared (FT-IR) Optimization of independent variable and FTIR spectra of Carvedilol (Pure API), validation lipid, cholesterol, ethanol, PG, OBE, Carbopol, Further Optimization to probe the Triethanolamine, and OBE-G are shown in Fig optimal formula of ethosomal suspension with 2.FTIR spectrum of Carvedilol showed peaks at desirable characteristics. This depended on the 3342.89 cm -1 which belongs to -N-H stretching, prescriptive criteria of minimum vesicle size, 2922.72 cm -1 which belong to -C-H stretching, maximum % EE and maximum cumulative % 1443 cm -1 which belong to C-C stretching, 1630 DR. The composition of the optimum cm -1 and 1607 cm -1 belong to C=C stretching formulation was found as 2 % of lipid (Soya and 1347 cm -1 to 1251 cm -1 belong to C-N lecithin), 20 % of ethanol and 10 % of PG. At stretching. All these characteristic peaks of these levels, the predicted values of Y1 (vesicle Carvedilol were present in OBE and also it was size), Y2 (% EE) and Y3 (Cumulative % drug found that there was no absence of any functional