The objective of the present research is to prepare stable nano suspensions of Valsartan (VAL) with high solubility and dissolution. VAL is an orally administered anti-hypertensive drug with lower bio-availability of 25%, this is attributed to its lower aqueous solubility (0.082 mg/ml). VAL nano suspensions were prepared by using a bottom-up precipitation technique using five level full factorial central composite design (CCD). The optimized nano formulations NS21, NS22, NS23 showed the particle size of 268.42±8.99, 288.3±11.32, 293.46±6.92 nm, zeta potential of 20.89±0.79, 26.01 ±1.02, 21.34±0.43 mVs and the dissolution efficiency of 93.10±1.459, 91.84±1.419, 89.47±0.644 % respectively. SEM & AFM studies represent the formation of fine irregularly shaped particles with smooth surfaces on nanosization. X-rd studies confirmed the physical state conversion of crystalline drug into amorphous form. Drug excipient compatibility was studied using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). The investigation pragmatic the solubility and dissolution efficiency of VAL in nanosuspension was significantly higher when compared with its pure form. Finally, it is concluded that, nanosuspension approach could be an ideal, promising approach to increase the solubility and dissolution of BCS-II drugs like Valsartan.
Background:
The hypothesis is to augment the bioavailability and therapeutic potential of low bioavailable
carvedilol (25-35%) through Nanostructured Lipid Carrier (NLC) loaded Transdermal patch (Nanolipid Transferosomes).
Methods:
Box-behnken design was designed to formulate NLC through hot homogenization technique. About 17
formulations (C1-C17) were formulated by varying the critical material attribute and critical process parameter.
Optimization was done based on its critical quality attributes like particle size; zeta potential; entrapment efficiency.
Selected NLC (C16) has been fabricated into a transdermal patch through solvent evaporation technique and estimated for
thickness; weight variation; moisture content; folding endurance; drug content; invitro drug release; ex-vivo skin
permeation studies 48hrs; in-vitro drug release kinetic studies and skin irritation studies. In-vivo pharmacokinetics and
pharmacodynamic study parameters were compared between carvedilol loaded NLC transdermal patch and a conventional
formulation (Coreg CR).
Results:
NLC (C16) was selected as the best formulation based on desirable, less particle size (201.1±2.02 nm); more zeta
potential (-37.2±1.84mV) and maximum entrapment efficiency (87.54±1.84%). Experimental investigations of in-vivo
dermatopharmacokinetic data shown a statistical significant changes (p<0.05) in the parameter (increased AUC0-α, MRT
with decreased Cmax, Tmax) when administered through transdermal patch and on compared to conventional dosage form. It
was observed that there was a significant changes with p <0.05 among the pharmacokinetic factors of conventional
Carvedilol formulation, Carvedilol NLC and Carvedilol NLC loaded Transdermal patch with a maximum time of peak
plasma concentration (Tmax) of 4hrs, 8hrs and 8hrs; maximum peak plasma concentration (Cmax) of 0.258 μg/ml, 0.208
μg/ml and 0.108 μg/ml. Area Under Curve (AUC0-α) was established to be 125.127 μg/ml/h, 132.576 μg/ml.h, 841.032 μg/ml.h, Mean Residence Time (MRT0- α
) of drug was established to be 17hrs, 19hrs and 82hrs respectively. This data
reveals the impact of NLC on the enhancement of bioavailability through transdermal patch. In-vivo pharmacodynamic
studies, confirms that NLC loaded transdermal patch (Nanolipid Transferosomes) shown a significant control in blood
pressure for 48 hrs when compared to conventional dosage form.
Conclusion:
This research data concludes that NLC loaded transdermal patch (Nanolipid Transferosomes) was a suitable
candidate to enhance the bioavailability of low bioavailable drug like Carvedilol.
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