Bandar E. Al-Dhubiab

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.

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.

Loratidine buccal films for allergic rhinitis: development and evaluation

Abstract The objective of this study was to develop a novel patient compliant buccoadhesive film capable of providing a prolonged protection against allergic symptoms. Polymeric buccoadhesive films of loratidine were prepared using hydroxypropylmethyl cellulose (HPMC)-E5 and K100 blend and Eudragit® NE 30D as retardant. Films were prepared using solvent-casting method. The developed films were evaluated for physical properties, hydration, mucoadhesion time, drug release, etc. All the prepared films exhibited excellent mechanical strength and uniform drug content. Increase in drug content did not influence the physicomechanical properties of the film. The mucoadhesive strength of films was significantly enhanced with increase in HPMC content. Increase in Eudragit® NE 30 D content in the film decreases the hydration, erosion and drug release, but enhances the mucoadhesion time. Furthermore, the release of loratidine from the prepared films followed Hixson–Crowell kinetics. Studies in healthy human volunteers using placebo films indicate that the prepared films possess prolonged mucoadhesion in-vivo, and this could potentially lead to clinically relevant drug delivery system.

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.

Understanding type 1 diabetes: etiology and models.

Type 1 diabetes is a complex disease involving a combination of factors, such as genetic susceptibility, immunologic dysregulation and exposure to environmental triggers. Animal models serve an important function both in elucidating the pathophysiology and preliminary screening of antidiabetic molecules. Hence, the development of models for type 1 diabetes can be broadly divided into 3 categories, namely: identification of spontaneously developing type 1 diabetes mellitus strains, creating diabetes-prone species through gene transfer techniques and forced destruction of islet cells through chemical or surgical means. This review discusses the models used to study type 1 diabetes with special emphasis on genetics.

Pharmaceutical applications and phytochemical profile of Cinnamomum burmannii.

Extensive studies have been carried out in the last decade to assess the pharmaceutical potential and screen the phytochemical constituents of Cinnamomum burmannii. Databases such as PubMed (MEDLINE), Science Direct (Embase, Biobase, biosis), Scopus, Scifinder, Google Scholar, Google Patent, Cochrane database, and web of science were searched using a defined search strategy. This plant is a member of the genus Cinnamomum and is traditionally used as a spice. Cinnamomum burmannii have been demonstrated to exhibit analgesic, antibacterial, anti-diabetic, anti-fungal, antioxidant, antirheumatic, anti-thrombotic, and anti-tumor activities. The chemical constituents are mostly cinnamyl alcohol, coumarin, cinnamic acid, cinnamaldehyde, anthocynin, and essential oils together with constituents of sugar, protein, crude fats, pectin, and others. This review presents an overview of the current status and knowledge on the traditional usage, the pharmaceutical, biological activities, and phytochemical constituents reported for C. burmannii.

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.

Evaluation of Halogenated Coumarins for Antimosquito Properties

Mosquitoes are the major vectors of parasites and pathogens affecting humans and domestic animals. The widespread development of insecticide resistance and negative environmental effects of most synthetic compounds support an interest in finding and developing alternative products against mosquitoes. Natural coumarins and synthetic coumarin analogues are known for their several pharmacological properties, including being insecticidal. In the present study halogenated coumarins (3-mono/dibromo acetyl, 6-halogenated coumarin analogues) were screened for larvicidal, adulticidal, and repellent properties against Anopheles arabiensis, a zoophilic mosquito that is one of the dominant vectors of malaria in Africa. Five compounds exerted 100% larval mortality within 24 h of exposure. All coumarins and halogenated coumarins reversibly knocked down adult mosquitoes but did not kill them after 24 h of exposure. Repellent properties could not be evidenced. Five compounds were considered potential larvicidal agents for further research and development, while adulticidal activity was considered only mild to moderate.

Design, synthesis, and computational studies on dihydropyrimidine scaffolds as potential lipoxygenase inhibitors and cancer chemopreventive agents

Dihydropyrimidine scaffold has a wide range of potential pharmacological activities such as antiviral, antitubercular, antimalarial, anti-inflammatory, and anticancer properties. 5-Lipoxygenase enzyme is an enzyme responsible for the metabolism of arachidonic acid to leukotrienes. The elevated levels of this enzyme and its metabolites in cancer cells have a direct relation on the development of cancer when compared to normal cells. The development of novel lipoxygenase inhibitors can have a major role in cancer therapy. A series of substituted 1,4-dihydropyrimidine analogues were synthesized and characterized by 1H-NMR, 13C-NMR, and HRMS. Molecular docking against lipoxygenase enzyme (protein data bank code =3V99) was done using Molecular Operating Environment 2013.08 and Leadit 2.1.2 softwares and showed high affinities. The synthesized compounds were tested for their lipoxygenase inhibitory activity and showed inhibition ranging from 59.37%±0.66% to 81.19%±0.94%. The activity was explained by a molecular docking study. The title compounds were also tested for cytotoxic activity against two human cancer cell lines Michigan Cancer Foundation-7 and human melanoma cells and a normal peripheral blood mononuclear cell line.