Drug Delivery Letters - Volume 10, Issue 2, 2020

Objective: Drug delivery through the nasal route is emerging as a promising approach due to its capability to transport the drug to the systemic circulation and the central nervous system for therapeutic benefits. Methods: In-situ gelling formulations comprising polymeric substances are emerging as preferential nasal drug delivery systems. When exposed to biological stimuli, they have the ability to undergo a solgel conversion. Result: Such mucoadhesive in-situ gel formulations designed and developed for the nasal administration have the ability to prolong the residence time of formulation in the nasal cavity, thereby serving better for complete uptake of the drug across the nasal mucosa. Conclusion: Thus, this review focuses on temperature-responsive, pH-responsive and ion responsive polymers utilized in the nasal in-situ gels together with their physicochemical characterization, evaluation and pharmaceutical applications.

Background: It has been observed that several diseases either acute or chronic have a specific symptom that is emesis. Emesis leads to depletion and removal of several salts and biological essentials required in the body. Domperidone is a D2 receptor antagonist, which triggers the chemoreceptor trigger zone (CTZ) and hence used in the management of nausea and vomiting. Objective: The objective of this project was to formulate a buccal patch of domperidone with the use of several polymers with a permeation enhancer. Since the oral bioavailability of domperidone is low due to gastric degradation, hence a buccal patch was prepared to determine its bioavailability. The purpose of this study was to formulate a buccal patch for better bioavailability and observe the effect of permeation enhancer with polymers. Methods: The mucoadhesive buccal patch was prepared using the solvent cast method. The characterization studies were done along with the drug content and compatibility studies through FTIR. Results: It was observed that the polymers; sodium carboxy methyl cellulose (SCMC) & polyvinyl alcohol(PVA) without sodium lauryl sulphate (SLS) had low drug release, which was around 68% and 72%, respectively whereas polymers with SLS had markedly increased drug release, which was around 89% and 91%, respectively. Conclusion: In order to obtain the maximum therapeutic efficacy of domperidone, buccal patches are considered much more beneficial than oral dosage form. Permeation enhancer also helps to synergize the effect of polymers which helps in better drug release and ultimately leads to better bioavailability.

Background: Paroxetine hydrochloride hemihydrate (PHH) is a serotonin reuptake inhibitor useful for the treatment of diverse psychiatric problems. Existing marketed formulations with frequent administration lead to gastrointestinal (GI) reactions and abrupt fluctuations in plasma level with poor patient compliance. These prerequisites are sufficed by controlled release push-pull osmotic pump tablets (PPOP). Objective: Objective of the present study was to develop robust and reliable PPOP formulation via Quality by design (QbD) approach to achieve desired release kinetics. Methods: PPOP was formulated using wet granulation method followed by osmotic coating. QbD strategy for defining the risk assessment of influential variables such as swelling polymers and osmogen on in vitro release kinetics of designed PPOP. Results: Presence of Polyox in push and pull layer along with osmogen controlled the drug release pattern from formulated PPOP system as depicted in 33 factorial design. These formulated optimized PPOP systems demonstrated 2 hrs lag time with zero-order kinetics, a peculiar feature of PPOPs. Conclusion: Scalable, stable PPOP tablets were fabricated by applying systematic QbD approach. The developed PPOP systems with improved concentration-independent behavior helped to address the challenges of existing marketed formulations. Risk mitigation and control strategy assured quality of the system during scalability. Application of QbD strategy in establishing the PPOP formulation would help in formulating drug candidates having gastric limitations and poor patient compliance. The present study is the detailed account of QbD based PPOP formulation, therefore it can be of potential importance from academics as well as industrial perspective.

Background: The oral administration route is still the most preferred by patients for drug treatment, but is unfortunately not suitable for all drug compounds. For example, protein and peptide drugs (e.g. insulin) are typically administered via injection seeing as they are unstable in the gastrointestinal luminal environment and have poor membrane permeation properties. To overcome this problem, functional excipients such as drug absorption enhancers can be co-administered. Although Aloe vera gel has the ability to improve the permeation of drugs across the intestinal epithelium, its drug permeation enhancing effect has not been investigated in the different regions of the gastrointestinal tract yet. Objective: The aim of this study was to investigate the insulin permeation enhancing effects of A. vera gel material across excised pig intestinal tissues from different regions of the gastrointestinal tract and to identify the gastrointestinal region where the highest insulin permeation enhancement was achieved. Methods: Insulin transport across excised pig intestinal tissues from the duodenum, proximal jejunum, medial jejunum, distal jejunum, ileum and colon was measured in the absence and presence of A. vera gel (0.5% w/v) using both the Sweetana-Grass diffusion chamber and everted sac techniques. Results: The insulin permeation results obtained from both ex vivo techniques showed varied permeation enhancing effects of A. vera gel as a function of the different regions of the gastrointestinal tract. The colon was identified as the gastrointestinal region where A. vera gel was the most effective in terms of insulin permeation enhancement in the Sweetana-Grass diffusion chamber technique with a Papp value of 5.50 x 10-7 cm.s-1, whereas the ileum was the region where the highest permeation enhancement occurred in the everted sac technique with a Papp value of 5.45 x 10-7 cm.s-1. Conclusion: The gastrointestinal permeation enhancing effects of A. vera gel on insulin is region specific with the highest effect observed in the ileum and colon.

Background: Cancer is one of the leading causes of death. New tactics targeting the survival pathways that provide effective drugs are being developed. Objective: Super paramagnetic nanoparticle serves as drug carrier for drug delivery system. Herein, Iron oxide-CMC-TA and Iron oxide-CMC-GA nanoparticles are synthesized for this target. Methods: Iron oxide (Fe2O3) nanoparticles are synthesized, bound to carboxymethyl chitosan (CMC) which are then conjugated to tartaric acid (TA) or gallic acid (GA) to form Iron oxide-CMC-TA and Iron oxide-CMC-GA nanoparticles. Those nanoparticles were characterized and the cytotoxicity effect was evaluated when associated with/without bee venom to measure the synergistic effect on A549 and WI-38 cell lines. In addition, apoptotic genes expression in A549 was evaluated when treated with both nanoparticles. Results: We showed that the cytotoxicity effect of TA and GA on A549 and WI-38 cell lines was increased when they immobilized on iron oxide-CMC nanoparticles and the effect was synergistically elevated when added to bee venom. The cytotoxic activity of these two nanoparticles was higher in A549 cancer cell line when compared with WI-38 normal cell line. Moreover, the expression of apoptotic genes was elevated. Conclusion: Iron oxide-CMC-TA nanoparticle and Iron oxide-CMC-GA nanoparticle can selectively induce apoptosis in cancer cell lines more than in normal cell lines, which is an important aspect in cancer cell targeting process to minimize damage upon normal cells.

Aims: The study was aimed to develop mucoadhesive buccal tablets using Aster ericoides leaves mucilage. Background: Mucilages are naturally occurring high-molecular-weight polyuronides, which have been extensively studied for their application in different pharmaceutical dosage forms. Objective: The objective of the present research was to establish the mucilage isolated from the leaves of Aster ericoides as an excipient for the formulation of the mucoadhesive buccal tablet. Methods: The mucilage was isolated from the leaves of Aster ericoides by maceration, precipitated with acetone and characterized. Tablets were prepared using wet granulation technique and evaluated for various official tests. Results: The mucilage was found to be non-toxic on A-431 and Vero cell lines. It was insoluble but swellable in cold and hot water. The results indicate that mucilage can form a three-dimensional network. The pH of the mucilage (6.82 ± 0.13) indicated that it might be non-irritant to the buccal cavity. The mucilage was found to be free from microbes. The release of drug was by Fickian diffusion. The in vivo buccal tablet acceptance was 80%. No significant difference between the diastolic blood pressure of standard and Aster tablets treated volunteer group was recorded. Conclusion: It might be concluded that the isolated mucilage from the leaves of Aster ericoides may be used as an excipient for the development of mucoadhesive buccal tablets. Other: However, to prove the potency of the polymer, in vivo bioavailability studies in human volunteers are needed along with chronic toxicity studies in suitable animal models.

Objective: Atorvastatin (ATV) is effective in reducing total cholesterol and low-density lipoprotein levels. Furthermore, it produces pleiotropic effects in neurodegenerative conditions such as Parkinson's, Alzheimer's, and epilepsy. However, due to the effective defense system of the central nervous system (CNS), the development of new medicines for clinical conditions has proven difficult. In this context, nanotechnology was applied as a promising solution to promote drug vectorization to the brain. Methods: The solvent emulsification-diffusion method was used to develop nanoparticles (NPs) based on polylactic acid and coated with polysorbate 80 containing ATV. Quality-by-Design (QbD) was used in the optimization of nanoparticles production through the application of the experimental design Box-Behnken Design. Results: After optimizing the independent factors including sonication time, surfactant concentration and surfactant volume, the NPs presented physicochemical characteristics such as entrapment efficiency of 86.4 ± 2.4%, mean size of 225.2 ± 4.8 nm, and zeta potential of -14.4 ± 0.36 mV. In the in vitro release study, approximately 20% of the encapsulated ATV was released. Conclusion: The application of QbD was very useful in demonstrating its applicability in the nanotechnological pharmaceutical area for controlling and predicting the influence of the variables in the production of NPs. The NPs developed in this study presented adequate physicochemical characteristics, which is promising for future in vivo studies. The physicochemical characteristics included entrapment efficiency of 86.4 ± 2.4%, mean size of 225.2 ± 4.8 nm, and zeta potential of -14.4 ± 0.36 mV. In the in vitro release study, approximately 20% of the encapsulated ATV was released. The application of QbD was very useful in demonstrating its applicability in the nanotechnological pharmaceutical area for controlling and predicting the influence of the variables in the production of NPs. The NPs developed in this study presented adequate physicochemical characteristics, which is promising for future in vivo studies.

Background and Objective: Bacopa monnieri, Evolvulus alsinoides, and Tinospora cordifolia are well known herbal Ayurvedic medicinal plants with a memory enhancing property. The aim of this study was HPTLC analysis for evaluating the effect of ethanolic extract of Bacopa monnieri (BME), Evolvulus alsinoides (EAE) and Tinospora cordifolia (TCE) alone and in combination of equal proportion (CEPs) against scopolamine-induced amnesic rats. Methods: HPTLC analysis was done to evaluate the presence of phytoconstituents in these plants. Morris water maze and passive avoidance tests were also used to evaluate the effect on memory function. All pretreatment with BME, EAE, TCE, and CEPs was done at 200 mg/kg. The observation was done on the basis of the effect on mean latency time (in seconds) in the Morris water maze test and latency to reach shock free zone (SFZ), mistakes in 15 minutes on the Passive-avoidance test. Results: It was observed that after HPTLC analysis, Bacoside A (Rf value; 0.82) found in BME, flavonoid glycoside (Rf value; 0.31) found in EAE and unknown compounds (Rf value; 0.11, 0.39) observed in TCE. BME, EAE, TCE and their combinations of equal proportion [CEP-1 (BME+EAE), CEP-2 (BME+TCE), CEP-3 (EAE+TCE) and CEP-4 (BME+EAE+TCE)] produced significant effects against scopolamine-induced amnesia in rats. Conclusion: These findings suggested that the content of extracts of these compounds has an antioxidant property in the brain. Also, BME, EAE, and TCE in the CEPs provide a synergistic effect on behavioral assessment.