33 research outputs found
Pharmacokinetic and pharmacodynamic features of nanoemulsion following oral, intravenous, topical and nasal route
Abstract: Background: Most of the active pharmaceutical ingredients discovered recently in pharmaceutical
field exhibits poor aqueous solubility that pose major problem in their oral administration. The oral administration
of these drugs gets further complicated due to their short bioavailability, inconsistent absorption and inter/intra
subject variability.
Methods: Pharmaceutical emulsion holds a significant place as a primary choice of oral drug delivery system for
lipophilic drugs used in pediatric and geriatric patients. Pharmacokinetic studies on nanoemulsion mediated drugs
delivery approach indicates practical feasibility in regards to their clinical translation and commercialization.
Results: This review article is to provide an updated understanding on pharmacokinetic and pharmacodynamic
features of nanoemulsion delivered via oral, intravenous, topical and nasal route.
Conclusion: The article is of huge interest to formulation scientists working on range of lipophilic drug molecules
intended to be administered through oral, intravenous, topical and nasal routes for vivid medical benefits.
Keywords: Hydrophobicity, oral delivery, pharmacokinetics, pharmacodynamics, routes of administration
Targeted drug delivery to the brain via intranasal nanoemulsion: available proof of concept and existing challenges
Intranasal delivery has shown to circumvent blood-brain-barrier (BBB) and deliver the drugs into the CNS at a higher rate and extent than other conventional routes. The mechanism of drug transport from nose-to-brain is not fully understood yet, but several neuronal pathways are considered to be involved. Intranasal nanoemulsion for brain targeting is investigated extensively. Higher brain distribution of drug after administering intranasal nanoemulsion was established by many researchers. Issues with nasomucosal clearance are solved by formulating modified nanoemulsion; for instance, mucoadhesive nanoemulsion or in situ nanoemulgel. However, no intranasal nanoemulsion for brain targeted drug delivery has been able to cross the way from ‘benches to bed-side’ of patients. Possibilities of toxicity by repeated administration, irregular nasal absorption during the diseased condition, use of a high amount of surfactants are few of the persisting challenges that need to overcome in coming days. Understanding the ways how current developments has solved some challenges is necessary. At the same time, the future direction of the research on intranasal nanoemulsion should be figured out based on existing challenges. This review is focused on the current developments of intranasal nanoemulsion with special emphasis on the existing challenges that would help to set future research direction
Promising drug delivery approaches to treat microbial infections in the vagina: a recent update
An optimal host–microbiota interaction in the human vagina governs the reproductive health status of a woman. The marked depletion in the beneficial Lactobacillus sp. increases the risk of infection with sexually transmitted pathogens, resulting in gynaecological issues. Vaginal infections that are becoming increasingly prevalent, especially among women of reproductive age, require an effective concentration of antimicrobial drugs at the infectious sites for complete disease eradication. Thus, topical treatment is recommended as it allows direct therapeutic action, reduced drug doses and side effects, and self-insertion. However, the alterations in the physiological conditions of the vagina affect the effectiveness of vaginal drug delivery considerably. Conventional vaginal dosage forms are often linked to low retention time in the vagina and discomfort which significantly reduces patient compliance. The lack of optimal prevention and treatment approaches have contributed to the unacceptably high rate of recurrence for vaginal diseases. To combat these limitations, several novel approaches including nano-systems, mucoadhesive polymeric systems, and stimuli-responsive systems have been developed in recent years. This review discusses and summarises the recent research progress of these novel approaches for vaginal drug delivery against various vaginal diseases. An overview of the concept and challenges of vaginal infections, anatomy and physiology of the vagina, and barriers to vaginal drug delivery are also addressed
Advancement on sustained antiviral ocular drug delivery for herpes simplex virus keratitis: recent update on potential investigation
The eyes are the window to the world and the key to communication, but they are vulnerable to multitudes of ailments. More serious than is thought, corneal infection by herpes simplex viruses (HSVs) is a prevalent yet silent cause of blindness in both the paediatric and adult population, especially if immunodeficient. Globally, there are 1.5 million new cases and forty thousand visual impairment cases reported yearly. The Herpetic Eye Disease Study recommends topical antiviral as the front-line therapy for HSV keratitis. Ironically, topical eye solutions undergo rapid nasolacrimal clearance, which necessitates oral drugs but there is a catch of systemic toxicity. The hurdle of antiviral penetration to reach an effective concentration is further complicated by drugs’ poor permeability and complex layers of ocular barriers. In this current review, novel delivery approaches for ocular herpetic infection, including nanocarriers, prodrugs, and peptides are widely investigated, with special focus on advantages, challenges, and recent updates on in situ gelling systems of ocular HSV infections. In general congruence, the novel drug delivery systems play a vital role in prolonging the ocular drug residence time to achieve controlled release of therapeutic agents at the application site, thus allowing superior ocular bioavailability yet fewer systemic side effects. Moreover, in situ gel functions synergistically with nanocarriers, prodrugs, and peptides. The findings support that novel drug delivery systems have potential in ophthalmic drug delivery of antiviral agents, and improve patient convenience when prolonged and chronic topical ocular deliveries are intended
Dendrimer entrapped microsponge gel of dithranol for effective topical treatment
Dithranol is one of the important topical agents for the treatment of psoriasis, a chronic inflammatory skin disease with aberrant differentiation of keratinocytes. However, its application is troublesome and inconvenient because of its associated side effects, including staining, burning sensation, irritation, and necrotizing effect on the diseased cells as well as on the normal cells. The purpose of the current investigation was to explore the potential of poly(amido) amine (PAMAM) dendrimers in the topical delivery of dithranol through a novel microsponge based gel. Generation-4 (G4) dendrimers were incorporated into the microsponge based gel formulation by quasi-emulsion solvent diffusion method with varying concentration of polymers, and evaluated for the morphology of the formulation, encapsulation efficiency and skin irritation potential. Percentage yield of the formulation was found to be 66.28%, whereas encapsulation efficiency was ranged between 71.33% to 49.21%, and an average particle size was ranged between 28 ± 1.12 μm to 130 ± 1.01 μm. Surface morphology of developed microsponge was confirmed by scanning electron microscopy, revealed micro-porous nature. The optimized microsponge formulation was found to be stable and recorded non-irritant during cutaneous application of the experimental animals. Further, the pharmacokinetic outcomes of study were showed prolong penetration of the drug through the skin, equivalent to the marketed formulation of dithranol. Therefore, it could be conferred that the microsponge formulation of the PAMAM entrapped dithranol can produce prolonged efficacy without producing toxicities to the skin, and thus can effectively be projected in the treatment of diseases like psoriasis
Development and validation of a high throughput LC–MS/MS method for simultaneous quantitation of pioglitazone and telmisartan in rat plasma and its application to a pharmacokinetic study
Management of cardiovascular risk factors in diabetes demands special attention due to their co-existence.
Pioglitazone (PIO) and telmisartan (TLM) combination can be beneficial in effective control of cardiovascular
complication in diabetes. In this research, we developed and validated a high throughput LC–MS/MS method for
simultaneous quantitation of PIO and TLM in rat plasma. This developed method is more sensitive and can
quantitate the analytes in relatively shorter period of time compared to the previously reported methods for their
individual quantification. Moreover, till date, there is no bioanalytical method available to simultaneously
quantitate PIO and TLM in a single run. The method was validated according to the USFDA guidelines for
bioanalytical method validation. A linear response of the analytes was observed over the range of 0.005–10 µg/mL
with satisfactory precision and accuracy. Accuracy at four quality control levels was within 94.27%–106.10%.
The intra- and inter-day precision ranged from 2.32% to 10.14% and 5.02% to 8.12%, respectively. The method
was reproducible and sensitive enough to quantitate PIO and TLM in rat plasma samples of a preclinical
pharmacokinetic study. Due to the potential of PIO-TLM combination to be therapeutically explored, this method
is expected to have significant usefulness in future
A randomized two-way crossover comparative pharmacokinetic study of two different tablet formulations containing ilaprazole in healthy human Indian volunteers
Background: Proton Pump Inhibitors (PPI) are observed to be great healer in gastroesophageal reflux disorder (GERD) and duodenal ulcer. Quantification of the drugs in human plasma by validated bioanalytical method are very important to determine pharmacokinetic parameters for undergoing comparative study with standard available formulations to make the newer one commercially available. Objective: The objective of this study was to determine the relative bioavailability of Ilaprazole, a novel PPI comparing the test formulation to the reference one according to standard regulatory guidelines. Materials and Methods: The bioequivalence of two tablet formulations, one as reference and other as test containing 10 mg of ilaprazole [CAS No. 172152-36-2] was studied in 12 healthy Indian volunteers. This was a single dose, twoperiod and randomized crossover study separated with a washout period of one week. Plasma samples for pharmacokinetic analysis were collected before dosing and at pre-specified time points after dosing. The concentration of ilaprazole in plasma was determined by a validated HPLC-UV method using theophylline as internal standard. The formulations were compared using the parameters Area under the plasma concentration-time curve (AUC 0-t ), Area under the plasma concentration-time curve from zero to infinity (AUC 0-͵), Peak plasma concentration (C max ), and time to reach peak plasma concentration (t max ). Results: Mean AUC 0-t of test and reference product were calculated to be 2627.793 ± 154.989 ng h ml−1 and 2555.905 ± 225.916 ng h ml−1 , with a C max of 347.459 ± 48.175 ng h ml−1 . While mean AUC 0-͵ of test and reference product were calculated to be 2733.334 ± 242.438 ng h ml−1 and 2728.716 ± 284.408 ng h ml−1 . Conclusion: The results of this investigation indicated no statistically significant differences between the logarithmic transformed AUC 0-͵ and C max values of the two preparations. The 90% confidence interval for the ratio of the logarithmic transformed AUC 0-t , AUC 0-͵ and C max were 2 within the bioequivalence limit of 80-125% and the relative bioavailability of test formulation was 102.81% to that of reference formulation. The results of this study in healthy human volunteers of 27.92 ± 5.12 yrs (average age), 171.28 ± 6.85 cm (average height) and 66.43 ± 5.21 kg (average weight) support the use of the 10 mg dose tablet newly formulated
Carbon nanotube scaffolds as emerging nanoplatform for myocardial tissue regeneration: a review of recent developments and therapeutic implications
Myocardial infarction (cardiac tissue death) is among the most prevalent causes of death among the cardiac patients due to the inability of self-repair in cardiac tissues. Myocardial tissue engineering is regarded as one of the most realistic strategies for repairing damaged cardiac tissue. However, hindrance in transduction of electric signals across the cardiomyocytes due to insulating properties of polymeric materials worsens the clinical viability of myocardial tissue engineering. Aligned and conductive scaffolds based on Carbon nanotubes (CNT) have gained remarkable recognition due to their exceptional attributes which provide synthetic but viable microenvironment for regeneration of engineered cardiomyocytes. This review presents an overview and critical analysis of pharmaceutical implications and therapeutic feasibility of CNT based scaffolds in improving the cardiac tissue regeneration and functionality. The expository analysis of the available evidence revealed that inclusion of single- or multi-walled CNT into fibrous, polymeric, and elastomeric scaffolds results in significant improvement in electrical stimulation and signal transduction through cardiomyocytes. Moreover, incorporation of CNT in engineering scaffolds showed a greater potential of augmenting cardiomyocyte proliferation, differentiation, and maturation and has improved synchronous beating of cardiomyocytes. Despite promising ability of CNT in promoting functionality of cardiomyocytes, their presence in scaffolds resulted in substantial improvement in mechanical properties and structural integrity. Conclusively, this review provides new insight into the remarkable potential of CNT aligned scaffolds in improving the functionality of engineered cardiac tissue and signifies their feasibility in cardiac tissue regenerative medicines and stem cell therapy