Sree Harsha

In vitro techniques to evaluate buccal films

Extensive research on transmucosal drug delivery in the past few decades has resulted in the clinical application of several drug molecules through the buccal route. Interestingly, most of the new chemical moieties under clinical trials are being screened for their potential to deliver through the buccal cavity. In this context, buccal film offers several advantages including convenient dosing and better patient compliance. However, the greatest challenge is to develop a high quality buccal film which also necessitates constant evaluation and understanding the performance of the dosage form, the critical steps to achieve a successful product development. Despite the intense focus on buccal film based drug delivery system, there are no official standardized methods for its evaluation. Significant efforts have been made to demonstrate and improve the efficacy, potency and safety of buccal film using in vitro, ex vivo and in vivo assessments. Besides the physical properties of the film, several other parameters such as residence time, mucoadhesion, drug release, in vitro and in vivo buccal permeation profiles and absorption kinetics of the drug are examined while characterizing the prepared buccal films. However, various research groups have employed different methods and experimental conditions to evaluate the formulation, which has limited the comparison of data between the research groups. This review provides an overview about the various parameters that are considered and assessed as a part of formulation development to ensure quality product with desired characteristics.

Ofloxacin targeting to lungs by way of microspheres.

The efficacy of drug candidates is frequently limited by their inability to reach the target site of action, especially when they are administered through conventional dosage forms or drug delivery systems. Targeted drug delivery systems have increased the amount of drug reaching the site and simultaneously decrease the amount being distributed to other parts of the body. Microspheres have emerged as a remedial measure to improve site-specific drug delivery to a considerable extent. As an application, lung-targeting albumin loaded ofloxacin microspheres (ALOME) were prepared by water in oil emulsion method. The appearance and size distribution were examined by scanning electron microscopy, and the aspects such as in vitro release characteristics, stability, drug loading, loading efficiency, pharmacokinetics and tissue distribution in albino mice were studied. The experimental results showed that the microspheres have an average particle size of 11.32 microm. The drug loading and loading efficiency were (66.95 and 94.8%) respectively. The in vitro release profile of the microspheres matched the Korsmeyers Peppas release pattern, and the release after 1h was 42%, while for the original drug, ofloxacin, under the same conditions, 90.02% released in the first half an hour. After intravenous administration (15 min), the drug concentration of microspheres group in lung of albino mice was 432 microg g(-1) while that of controlled group was 1.32 microg g(-1) ALOME found to release the drug to a maximum extent in the target tissue, lung. Histopathological studies proved the tissue compatibility of ALOME to be safe.

Formulation and evaluation of nano based drug delivery system for the buccal delivery of acyclovir

Oral bioavailability of acyclovir is limited, primarily because of low permeability across the gastrointestinal membrane. The purpose of this study is the prospective evaluation of buccal films impregnated with acyclovir loaded nanospheres as a drug delivery system to improve systemic bioavailability. Acyclovir polymeric nanospheres were prepared by double emulsion solvent evaporation technique. Nanospheres were embedded into buccoadhesive films (A1-A4) comprising of different concentrations of polymers (Eudragit RL 100, HPMC K15 and carbopol 974P). Films were characterized for physico-mechanical properties, mucoadhesive strength, hydration, drug release and ex vivo permeation. In vivo studies were carried out on rabbits to assess the pharmacokinetic profile of buccal film (A3) as compared to oral therapy. The prepared films demonstrated excellent physical properties, adequate hydration and buccoadhesive strength. In vitro drug release data inferred that the drug release was dependent on the composition of film. Ex vivo permeation studies indicated greater flux in film A3. In vivo studies revealed a significant enhancement in absorption of acyclovir (P<0.0001) with Cmax (~3 folds) and AUC0-α (~8 folds, P<0.0001) when compared to oral dosing. Moreover, the extended Tmax value (6h) signifies the potential of the prepared film to prolong acyclovir delivery. Given the promising results, the study concludes that the developed buccal film (A3) impregnated with acyclovir loaded nanospheres could be a promising approach for effective delivery of acyclovir.

Enhanced oral bioavailability of acyclovir by inclusion complex using hydroxypropyl-β-cyclodextrin

Abstract The therapeutic potential of acyclovir is limited by the low oral bioavailability owing to its limited aqueous solubility and low permeability. The present study was a systematic investigation on the development and evaluation of inclusion complex using hydroxypropyl-β-cyclodextrin for the enhancement of oral bioavailability of acyclovir. The inclusion complex of acyclovir was prepared by kneading method using drug: hydroxypropyl-β-cyclodextrin (1:1 mole). The prepared inclusion complex was characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, NMR spectroscopy and evaluated in vitro by dissolution studies. In vivo bioavailability of acyclovir was compared for inclusion complex and physical mixture in rat model. Phase solubility studies indicate the formation of acyclovir–hydroxypropyl-β-cyclodextrin complex with higher stability constant and linear enhancement in drug solubility with increase in hydroxypropyl-β-cyclodextrin concentration. Characterization of the prepared formulation confirms the formation of acyclovir–hydroxypropyl-β-cyclodextrin inclusion complex. Dissolution profile of inclusion complex demonstrated rapid and complete release of acyclovir in 30 min with greater dissolution efficiency (90.05 ± 2.94%). In vivo pharmacokinetic data signify increased rate and extent of acyclovir absorption (relative bioavailability ∼160%; p < 0.0001) from inclusion complex, compared to physical mixture. Given the promising results in the in vivo studies, it can be concluded that the inclusion complex of acyclovir could be an effective and promising approach for successful oral therapy of acyclovir in the treatment of herpes viruses.

Sensibility of male rats fertility against olive oil, Nigella sativa oil and pomegranate extract

OBJECTIVE To clarify the modulatory effects of daily consumption of pomegranate extract (PE), olive oil (OO) and Nagilla sativa oil (NSO) on antioxidant activity, sperm quality and pituitary-testicular axis of adult male wistar rats. METHODS Thirty-two adult male Wistar rats were divided into four equal groups, eight rats each. Using rat gastric tubes, 1.0 mL distilled water, 1.0 mL PE, 0.4 mL NSO and 0.4 mL OO were orally administered daily for 6 weeks in the first, second, third and fourth groups, respectively. Reproductive organs, body weight, sperm criteria, testosterone, FSH, LH, inhibin-B, lipid peroxidation, and antioxidant enzyme activities were investigated. At the end of the study protocol, analyses occurred at the same time. Data were analysed by ANOVA test and P<0.05 was considered to be a significant value. RESULTS In all studied groups, malondialdehyde level was significantly decreased accompanied with an increases in glutathione peroxidase and glutathione. Rats treated with PE showed an increase in catalase activities accompanied with an increase in sperm concentration which was also observed in NSO group. In PE treated group, sperm motility was also increased accompanied with decreased abnormal sperm rate. NSO, OO and PE treated groups shows an insignificant effect on testosterone, inhibin-B, FSH and LH in comparison with control group. CONCLUSIONS These results show that administration of PE, NSO and OO could modify sperm characteristics and antioxidant activity of adult male wistar rats.

High-performance thin layer chromatography: A powerful analytical technique in pharmaceutical drug discovery.

Analysis of pharmaceutical and natural compounds and newer drugs is commonly used in all the stages of drug discovery and development process. High-performance thin layer chromatography is one of the sophisticated instrumental techniques based on the full capabilities of thin layer chromatography. The advantages of automation, scanning, full optimization, selective detection principle, minimum sample preparation, hyphenation, and so on enable it to be a powerful analytical tool for chromatographic information of complex mixtures of pharmaceuticals, natural products, clinical samples, food stuffs, and so on.

Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization.

Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology – the Büchi Nano Spray Dryer B-90 – and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm3. In vitro drug release of formulations was best fitted by first-order and Peppas models with R2 of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25°C ± 2°C and 60% ± 5% relative humidity.

Nanoparticle formulation by Büchi B-90 Nano Spray Dryer for oral mucoadhesion

Diabetes is considered one of the main threats to global public health in this era. It is increasing rapidly in every part of the world; the prevalence of the disease will grow to the point where 366 million people will be affected by 2030. The prevalence of diabetes mellitus (DM) in the Saudi population is high, and the majority of patients suffer from type 2 DM. Marketed oral antidiabetic drugs have indicated poor tolerability during chronic treatments, and this contributes to the moderately large proportion of type 2 DM patients that remain inadequately managed. Vildagliptin nanospheres were prepared with aminated gelatin using a spray-drying method; narrow particle-size distribution was seen at 445 nm. The angle of repose was found to be θ <33.5°. The nanospheres appeared to be spherical with a smooth surface. The drug content and percentage yield of the nanospheres were found to be 76.2%±4.6% and 83%±2%, respectively. The nanosphere-swell profile was found to be 165%±7%. The pure drug was 100% dissolved in 30 minutes, and the nanosphere formulation took 12 hours to dissolve (97.5%±2%), and followed a Korsmeyer–Peppas kinetic model with an R2 of 0.9838. The wash-off test of nanospheres found that they exhibited an excellent mucoadhesive property at 86.7% for 8 hours. The stability-study data showed no changes in the physicochemical properties of the nanospheres, and suggested that the nanospheres be stored below room temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours).

Development and evaluation of buccal films impregnated with selegiline-loaded nanospheres

Abstract Poor peroral therapeutic efficiency of selegiline is primarily due to the extensive hepatic metabolism and hence the need for an alternative route of administration. The present study is based on evaluation of a buccal film which is impregnated with selegiline nanospheres to enhance the systemic bioavailability. Selegiline-loaded nanospheres prepared using poly(lactide-co-glycolide) was embedded into buccal films (F1–F4) with varying polymer composition [hydroxypropyl methylcellulose and eudragit]. The developed films were evaluated for their physicomechanical properties, hydration, mucoadhesive strength, in vitro drug release and ex vivo permeation in order to identify the ideal system suitable for further development. In vivo studies were carried out on rabbits to assess the comparative pharmacokinetics profile of the selected buccal film with oral solution. Preliminary studies indicated that the prepared films exhibited excellent physical properties, adequate mucoadhesive strength and moderate hydration. In vitro drug release data of the buccal films (F1, F2 and F3) showed distinct profiles. Permeation studies indicated higher steady-state flux from film F3 (p < 0.0001) when compared to film F2. In-vivo results of film (F3) demonstrated significant increase in absorption (p < 0.0001), Cmax (∼1.6-fold), Tmax, AUC0–α (∼3-fold, p < 0.0001) and improved bioavailability, when compared to control. This study concludes that the buccal delivery of selegiline using the developed buccal film (F3) would be a promising alternative approach for the treatment of Parkinsons disease.

Design and formulation of mucoadhesive microspheres of sitagliptin

Mucoadhesive microspheres of sitagliptin (SITCM), a new anti-diabetic drug was prepared with carbopol 934 P using Buchi B-90 nano spray drier and optimized to analyse the key effects and relations of three factors on formulation of SITCM were studied. The appearance of the microspheres was found to be shriveled to nearly spherical, with a narrow size of 2–8 µm. The drug loading and percentage yield was found to be 73 ± 0.2% and 92 ± 0.3%, respectively. In vitro release indicated Korsmeyer–Peppas pattern mucoadhesion of SITCM-8 was found to be 7.8 ± 0.3 h. In vivo studies in rats suggest that the sitagliptin was retained in the gastrointestinal tract for an extended period of time (∼12 h) and control group was reduced significantly (∼4 h). This study concludes that the mucoadhesive microsphere could be one of the most appropriate drug delivery approaches for the successful delivery of sitagliptin.