SECOND-ORDER DERIVATIVE UV SPECTROPHOTOMETRIC AND RP-HPLC METHODS FOR THE ANALYSIS OF VILDAGLIPTIN AND APPLICATION FOR DISSOLUTION STUDY

This study describes two analytical methods, by second-order derivative UV spectrophotometric by HPLC, for determination of vildagliptin, a drug used for treatment of type 2 Diabetes Mellitus that belongs to a therapeutic class called inhibitors of dipeptidyl peptidase 4. The methods were validated in accordance with ICH and USP requirements. Analyses by UV derivative method were performed at 220 nm, which was the zero crossing point of excipient solutions. HPLC was optimized and the analysis was carried out using a Zorbax Eclipse Plus RP-C8 column (150 mm × 4.6 mm, 5 μm), detection at 207 nm, and potassium phosphate buffer solution pH 7.0 : acetonitrile (85:15, v/v) as mobile phase. In dissolution test, the conditions used were 0.01 mol L-1 hydrochloric acid in 900 mL of dissolution medium, USP apparatus 2 (paddle) and 50 rpm stirring speed. Both methods were successfully applied for analysis of dissolution samples from marketed vildagliptin tablets

Development and validation of a dissolution test for empagliflozin in film-coated tablets

The present study proposes a validated dissolution method for empagliflozin (EMPA) in film coated tablets. A gradual in vitro dissolution profile for this formulation was obtained using 900 mL of hydrochloric acid 0.01 M at 37 °C ± 0.5 °C as dissolution medium and USP apparatus 2 (paddle) at 50 rpm. The dissolved percentage of EMPA was quantified by ultraviolet spectrophotometric method to obtain cost technique and produce little residual solvents. Validation parameter for dissolution methodology such as the specificity, linearity, accuracy and precision were evaluated according to the international guidelines, giving results within the acceptable range. The method is linear in the range of 1 - 40 µg/mL, precise, with RSD value less than 2.62%, accurate (mean recovery 106.97%) and robust. Therefore, since no official method has been described, the proposed dissolution conditions represent a relevant contribution to evaluate the dissolution profile of coated tablet containing 25 mg of EMPA

Media for nimesulide tablet dissolution: surfactant action

A nimesulida é um antiinflamatório não-esteróide com baixa solubilidade em água e caráter fracamente ácido. O desenvolvimento dos ensaios de dissolução para fármacos de baixa hidrossolubilidade pode ser problemático e tensoativos são freqüentemente requeridos para aumentar a solubilização dos mesmos. No presente trabalho avaliou-se o efeito dos tensoativos lauril sulfato de sódio e polissorbato 80, na promoção da solubilidade da nimesulida em meio aquoso, determinando-se também o pH, a tensão superficial e a concentração micelar crítica dos meios testados. A nimesulida apresentou baixa solubilidade nos meios sem tensoativos (;300 mg/mL) foram observadas em tampão fosfato pH 7,4 com polissorbato 80. A concentração de saturação do fármaco aumentou proporcionalmente com a concentração dos tensoativos, os quais atuam pelo mecanismo de solubilização micelar. Obtiveram-se perfis de dissolução de três formulações de comprimidos de nimesulida, em meios com diversas concentrações de tensoativo, empregando-se o aparelho de dissolução com agitador de pá. Os resultados mostraram que a escolha do meio de dissolução para nimesulida deve ser criteriosa, de modo a evitar condições de baixo poder discriminante das formulações.Nimesulide is a non-steroidal anti-inflammatory drug, which presents low water-solubility and weak-acid properties. The intrinsic solubility of a drug plays an important role on drug dissolution from a solid dosage form. The development of a dissolution test for poorly hydrophilic drugs can exhibit some difficulties and surfactants are often used to promote drug solubilization. In this work the influences of both sodium laurylsulfate and polysorbate 80 on promotion of nimesulide aqueous solubility were studied. The media were also evaluated regarding their pH, surface tension and critical micelle concentration. All media without surfactant gave very low nimesulide solubility (;300 mg/mL) were got in phosphate buffer pH 7.4 with polysorbate 80 as additive. As surfactant concentration increases, higher drug saturation values are obtained by micellar solubilization. Dissolution profiles of three nimesulide tablets formulations were conducted employing media with different surfactant concentration by the rotating paddle-method. The results indicated that surfactants in nimesulide dissolution studies should be criteriously chosen in order to avoid poor discriminating medium characteristics

Development of nanoemulsions containing penciclovir for herpes simplex treatment and a liquid chromatographic method to drug assessment in porcine skin layers

A successful formulation (penciclovir hydrogel nanoemulsion - HN) to be used in transdermal drug delivery route to treat herpes simplex virus was developed and an analytical method to quantify penciclovir (PCV) in porcine ear skin was stablished and validated. PCV nanoemulsions were prepared by high pressure homogenization and presented spherical mean droplet size 180 nm. The association efficiency and zeta potential were 87% and– 27 mV, respectively. The bioanalytical method developed showed specificity for the interferences from the skin matrixes (epidermis and dermis) and the linearity was in the range 0.1 – 25 μg/mL of drug, The mean recovery data for the three levels tested were 95.2% for the epidermis and 97.3% for the dermis and adequate results were obtained for repeatability and inter-day precision.  In vitro percutaneous absorption studies with the PCV nanoemulsion and a market cream were conducted employing the porcine skin.The cumulative amounts of PCV permeated from cream and HN, 8 h after dosing, were 2.60 and 4.15 μg/cm², respectively, representing a quite higher flux and a much higher permeability coefficient for the developed formulation. It can be concluded that HN provide a good skin targeting effect and may be a promising carrier for topical delivery of penciclovir

In vitro evaluation of cutaneous penetration of acyclovir from semisolid commercial formulations and relation with its effective antiviral concentration

The evaluation of drug permeation/penetration of semisolid formulations into animal skin can be useful to supplement the pharmaceutical equivalence. This paper describes the in vitro assessment of acyclovir (ACV) into porcine skin from commercial formulations with etermination of drug concentration in different layers of cutaneous tissue to correlate with effective antiviral concentration in order to improve the equivalence decision. Studies were conducted using Franz cells and porcine skin. Selected pharmaceutical creams containing ACV had identical (reference and generic) and different (similar) excipients. A software program was employed for the simulation of antiviral effectiveness in the skin. Regarding ACV skin penetration, the first batch of the generic product showed a significant difference from reference and similar products, while in the second batch all products demonstrated equivalent drug penetration in the skin. Simulation studies suggest that formulations analysed exhibit a pharmacological effect even when in contact with Herpes simplex strains of high IC50 (inhibitory concentration required to reduce viral replication by 50%). According to results, it can be assumed that the in vitro cutaneous permeation/penetration study does not supply sensitivity information regarding small alterations of ACV semisolid formulations due to the variability inherent to the method, although it can be relevant to pharmaceutical equivalence studies in the development of semisolid products