Transdermal Evaporation Drug Delivery System: Concept to Commercial Products

Since two decades or so transdermal route established itself as better alternative to traditional oral route. This is possible due to continuous innovations in transdermal drug delivery (TDD), which not only enables researchers from academia and industry to successfully develop and launch many new pharmaceuticals but also allow to include new classes of drugs that can be developed into transdermal formulations. These successes are achieved due to the use of novel techniques based on either physical or chemical approaches. However, both of these techniques suffer due to their own disadvantages. Comparatively, a simple method of supersaturation to enhance drug permeation across skin has created a new wave of interest. Even though the application supersaturated principle in topical and TDD has been used from 1960s, but proper control of drug release and formation of stable supersaturated states has been the core of intense research in the last decade. Out of various methods used to get supersaturated system, evaporation method is considered as most efficient and practically feasible for TDD. Therefore, in this review concept of supersaturation, selection of solvent system and the mechanism of inhibition of crystallization are discussed. Application of evaporation systems in the development of transdermal formulations such as solutions, semisolids and metered dose therapeutic systems (MDTS) and the commercial evaporative systems are also discussed in this review

Antimicrobial activity assessment of time-dependent release bilayer tablets of amoxicillin trihydrate

O objetivo do presente estudo foi avaliar a atividade antimicrobiana de formulações de comprimidos de dupla camada contendo amoxicilina triidratada para liberação tempo dependente e avaliação da liberação in vitro do fármaco pelo ensaio de atividade antimicrobiana utilizando o método de difusão em placa de ágar. Os comprimidos de dupla camada consistem em uma camada para liberação retardada e outra sustentada. O método de compressão direta foi usado para a preparação dos comprimidos de dupla camada contendo Eudragit-L 100 D55 como polímero para liberação retardada e HPMCK4M ou HPMCK15 como polímeros para liberação sustentada. As formulações de comprimidos de dupla camada contendo amoxicilina triidratada foram avaliadas quanto a dureza, espessura, friabilidade, variação de peso e conteúdo de fármaco. Além disso, a liberação do fármaco in vitro foi avaliada por ensaio de atividade antimicrobiana usando S. aureus e E. coli como microrganismos teste. A alíquota das amostras do estudo de liberação do fármaco in vitro demonstrou ser efetiva contra ambos os microrganismos por um período de 16 horas devido à ação sustentada. O estudo de liberação do fármaco in vitro e o ensaio de atividade antimicrobiana mostraram que os comprimidos de dupla camada tiveram um perfil de liberação sustentada do fármaco com um pico de liberação após 2 horas de ensaio. O menor valor de MIC (2 ug/mL) dos comprimidos de dupla camada quando comparados à formulação comercial (5 ug/mL) representa uma boa atividade antimicrobiana.The aim of present study was the assessment of antimicrobial activity of prepared time-dependent release bilayer tablets of amoxicillin trihydrate and in vitro evaluation of drug release by antimicrobial assay using agar plate diffusion method. The bilayer tablets comprised of a delayed and sustained release layer. Direct compression method was used for the preparation of bilayer tablets containing Eudragit-L100 D55 as delayed release polymer, and HPMCK4M and HPMCK15 as sustained release polymers. The prepared bilayer tablets containing amoxicillin trihydrate were evaluated for hardness, thickness, friability, weight variation and drug content. Further, in vitro drug release was assessed by antimicrobial assay using S. aureus and E. coli as test microorganisms. The aliquot samples of in vitro drug release study were found to be effective against both microorganisms for 16 hours due to sustained action. The in vitro drug release study and antimicrobial assay showed that bilayer tablets have sustained release profile of drug delivery with time-dependent burst release after a lag-time of 2 hours. The lower MIC value (2 µg/mL) of prepared bilayer tablets vis-à-vis marketed preparation (5 µg/mL) represented its good antimicrobial activity

NEUROPROTECTIVE ACTIVITY OF FRACTIONAL FLOWER EXTRACTS OF MIRABILIS JALAPA AGAINST ALUMINIUM HYDROCHLORIDE INDUCED NEUROTOXICITY IN MALE WISTER RATS

Objective: The major objective of this present study was to evaluate the neuroprotective effect of fractional flower extracts (acetone, petroleum ether, methanol and aqueous) of Mirabilis jalapa (MJ) against aluminium hydrochloride-induced neurotoxicity in male wister rats.Methods: From the different fractional flower extracts of Mirabilis jalapa (MJ), two doses (250 and 500 mg/kg body weight) of each extract was initially selected and administered per orally 30 min prior to aluminium hydrochloride administration to the different animal groups once a day for a period of 45 d. Rat serum was collected from different animal groups on 1st, 15th, 30th and 45th days for estimation of marker enzymes, where a reduction in marker was observed. Animal was sacrificed by decapitation and the whole brain of rats was analyzed to estimate the levels of nitrite, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (DOS), catalase, reduced glutathione and acetylcholinesterase (AchE).Results: On the 9th day the Wister rats were sacrificed and cerebral cortex was removed. One-half of the cerebral cortex samples from different groups of Aluminium hydrochloride treated rats were stored in FAM mixture (40% formaldehyde, acetic acid and methanol in the ratio of 1:1:8) for histological analysis. From the study confirmed that dose of 250 and 500 mg/kg bwt of methanolic extract of MJ significantly (p˂0.001) increases the reduced glutathione, superoxide dismutase and catalase level, whereas petroleum ether, acetone and aqueous fractional flower extracts of MJ significantly (p˂0.01) decreases nitrite, TBARS and AchE levels of aluminium hydrochloride treated groups.Conclusion: This result is indicating evidence for Mirabilis jalapa had a significant neuroprotective effect on aluminium hydrochloride-induced neurotoxicity and also supports by histopathological studies

Design of experiments assisted the development of inclusion complexes of ramipril using hydrophilic carriers for enhancement of solubility and dissolution rate

Abstract The goal of the present study was to develop inclusion complexes and polymers dispersions of ramipril prepared by physical mixing, kneading, co-evaporation, and solvent evaporation methods to enhance drug solubility and dissolution rate, and thereby to reduce drug dose and side effects using selected hydrophilic carriers such as β-CD, PVP-K25, PEG 4000, and HPMC K100M. The prepared formulations were characterized for solubility and in-vitro drug release studies. The systematic optimization of formulations was performed using I-Optimal experimental design by selecting factors such as type of carriers (X1), drug: carrier ratio (X2), and method of preparation (X3), and response variables including percent yield (Y1), solubility (Y2), Carr’s index (Y3) and drug release in 30 min (Y4). Mathematical modeling was carried out using a quadratic polynomial model. The inclusion complex formulation (F27) was selected as an optimized batch by numerical desirability function and graphical optimization with the help of design space. The inclusion complex prepared by the co-evaporation method showed maximum drug solubility and released in pH 6.8 phosphate buffer compared to pure and other formulations. The inclusion complex is a feasible approach to improve the solubility, dissolution rate, bioavailability, and minimization of drugs’ gastrointestinal toxicity upon oral administration of ramipril

Design of experiments assisted the development of inclusion complexes of ramipril using hydrophilic carriers for enhancement of solubility and dissolution rate

The goal of the present study was to develop inclusion complexes and polymers dispersions of ramipril prepared by physical mixing, kneading, co-evaporation, and solvent evaporation methods to enhance drug solubility and dissolution rate, and thereby to reduce drug dose and side effects using selected hydrophilic carriers such as β-CD, PVP-K25, PEG 4000, and HPMC K100M. The prepared formulations were characterized for solubility and in-vitro drug release studies. The systematic optimization of formulations was performed using I-Optimal experimental design by selecting factors such as type of carriers (X1), drug: carrier ratio (X2), and method of preparation (X3), and response variables including percent yield (Y1), solubility (Y2), Carr’s index (Y3) and drug release in 30 min (Y4). Mathematical modeling was carried out using a quadratic polynomial model. The inclusion complex formulation (F27) was selected as an optimized batch by numerical desirability function and graphical optimization with the help of design space. The inclusion complex prepared by the co-evaporation method showed maximum drug solubility and released in pH 6.8 phosphate buffer compared to pure and other formulations. The inclusion complex is a feasible approach to improve the solubility, dissolution rate, bioavailability, and minimization of drugs’ gastrointestinal toxicity upon oral administration of ramipril

Generalized Interacting Dark Energy Model and Loop Quantum Cosmology

The recently observed accelerated expansion of the universe has put a challenge for its theoretical understanding. As a possible explanation of this, it is considered that the most part of the present universe is filled with a form of energy that exerts a negative pressure called dark energy, which drives the acceleration. In the present work, we assume a dynamical dark energy model, where dark energy interacts with matter and grows at the expense of the latter. Using this model, we discuss the evolution of the universe within the context of loop quantum cosmology. Our work successfully explains the presently observed accelerated expansion of the universe, by predicting that the present universe is phantom dominated. We also found that in the past, the expansion of the universe was decelerated one and transition from deceleration to acceleration would occur at $t_{q=0}=0.688t_0$, where $t_0$ is the present age of the universe. Again, our analysis predicted that at the transition time, the universe would be dominated with quintessence type dark energy.Comment: Accepted for publication in Astrophysics and Space Science Journal having the manuscript number ASTR-D-21-00429R

BOX-BEHNKEN DESIGN-BASED DEVELOPMENT AND CHARACTERIZATION OF POLYMERIC FREEZE-DRIED NANOPARTICLES OF ISRADIPINE FOR IMPROVED ORAL BIOAVAILABILITY

Objective: This study aimed to develop and optimize Isradpine-loaded polymeric freeze-dried nanoparticles prepared by solvent shifting method with the help of the experiment design for improving oral drug bioavailability and minimizing dosing intervals. Methods: Isradipine is a potent anti-hypertensive drug that is matrixed in polymeric freeze-dried nanoparticles using solvent shifting. In this work, a 3-factor, 3-level Box-Behnken design was used to optimize the process parameters like a drug: PLA concentration (A), poloxamer 407 concentration (B), and stirring speed (C). In addition, responses were measured as dependent variables such as percentage drug release, particle size (nm), Zeta potential (mV), and % entrapment efficiency. Results: Mathematical equations and response surface plots were used to relate the dependent and independent variables. The optimization model exhibited 97.36 % drug release, 153.14 nm particle size, -25.9 mV Zeta potential, and 78.25% entrapment efficiency, respectively. The observed responses were in close agreement with the predicted values of the optimized process. Fourier transform infrared spectroscopy, morphological studies, and in-vitro drug release studies characterized the prepared polymeric nanoparticles. Conclusion: The improved freeze-dried polymeric nanoparticle samples exhibited an in vitro drug release rate of more than 90% at 24h. Based on in vivo pharmacokinetic parameters, the isradipine-loaded polymeric nanoparticles show better bioavailability than pure drug's suspension form

QUALITY BY DESIGN DRIVEN FORMULATION DEVELOPMENT, AND OPTIMIZATION OF ENALAPRIL MALEATE LOADED MUCOADHESIVE MICROSPHERES: IN-VITRO AND IN-VIVO CHARACTERIZATION

Objective: The study is to formulate the enalapril maleate-loaded mucoadhesive microspheres with varied compositions of selected polymers for developing the oral controlled release formulations prepared by ionic gelation method and optimization through central composite design. Methods: Systematic optimization of microspheres was accomplished by central composite design and characterized for particle size, entrapment efficiency, in vitro drug release and ex vivo mucoadhesion strength, which indicated that microspheres were consequence to be spherical and free flowing in nature. The microspheres exhibited high drug entrapment efficiency and in vitro drug release in a sustained manner, which was considered to be dependent on the concentration of rate controlling polymers. The microspheres are showed 389.2 to 850µm particle size and 22.36 to 85.22 % encapsulation efficiency. In-vitro studies indicated optimized formulation showed 89.26% drug release after 12h and reduced blood pressure effectively. Results: The pharmacokinetic parameters were evaluated with Cmax of 75.39 µg/ml, tmax of 8h, and AUC of 53.55 µg/hr/ml, elimination rate constant of 0.0392 and t1/2 of 10h. The stability studies were conducted for 3 months under various conditions and identified no significant deviations in selected key quality attributes.   Conclusion: The formulated mucoadhesive microspheres of enalapril maleate tend to reduce the blood pressure in the animal model, with the novel drug delivery approach in the efficient management of hypertension

QbD-based design and characterization of mucoadhesive microspheres of quetiapine fumarate with improved oral bioavailability and brain biodistribution potential

The present work aims to discuss on Quality by Design based development and characterization of the sustained release mucoadhesive microspheres of quetiapine fumarate. The microspheres were prepared by non-aqueous solvent evaporation process. Factor screening study was carried out using fractional factorial design for identifying the influential factors. Systematic optimization of microspheres was accomplished by Box-Behnken design and characterized for particle size, entrapment efficiency, in vitro drug release and ex vivo mucoadhesion strength, which indicated that microspheres were consequence to be spherical and free flowing in nature. The microspheres exhibited high drug entrapment efficiency and in vitro drug release in a sustained manner, which was considered to be dependent on the concentration of rate controlling polymers. Ex vivo wash-off test on microspheres indicated good mucoadhesive property on excised goat intestinal mucosa. Out of all the accepted formulation, F6 was preferred as the optimized formulation. In vivo pharmacokinetic and brain biodistribution study revealed significant increase in the levels of drug in blood plasma and brain homogenates from the optimized formulation vis-à-vis the pure drug suspension. Overall, current study corroborated significant improvement in the biopharmaceutical attributes of quetiapine fumarate from mucoadhesive microspheres, which can be effectively used for management of depression and schizophrenia. Keywords: Quality by Design, DoE, Sustained release, Mucoadhesion, Depressio