Bhupendra G. Prajapati

Effect of hydrophilic polymers on buccoadhesive Eudragit patches of propranolol hydrochloride using factorial design.

The purpose of this study was to develop formulations and systematically evaluate in vitro performances of buccoadhesive patches of propranolol hydrochloride using the hydrophobic polymer Eudragit L-100 as the base matrix. The hydrophilic polymers Carbopol 934 and polyvinyl pyrrolidone (PVP) K30 were incorporated into the Eudragit patches, to provide the patches with bioadhesive properties and to modify the rate of drug release. The patches, which were prepared by the solvent casting method, were smooth and elegant in appearance; were uniform in thickness, weight, and drug content; showed no visible cracks; and showed good folding endurance. A 32 full factorial design was employed to study the effect of independent variables like hydrophilic polymers Carbopol 934 and PVP K30, which significantly influenced characteristics like swelling index, ex vivo mucoadhesive strength, in vitro drug release, and ex vivo residence time. A stability study of optimized Eudragit patches was done in natural human saliva; it was found that both drug and buccal patches were stable in human saliva. It can be concluded that the present buccal formulation can be an ideal system to improve the bioavailability of the drug by avoiding hepatic first-pass metabolism.

Formulation, evaluation, and comparison of bilayered and multilayered mucoadhesive buccal devices of propranolol hydrochloride

The purpose of this research work was to establish mucoadhesive buccal devices of propranolol hydrochloride (PRH) in the forms of bilayered and multilayered tablets. The tablets were prepared using sodium carboxymethylcellulose (SCMC) and Carbopol-934 (CP) as bioadhesive polymers to impart mucoadhesion and ethyl cellulose (EC) to act as an impermeable backing layer. Buccal devices were evaluated by different parameters such as weight uniformity, content uniformity, thickness, hardness, surface pH, swelling index, ex vivo mucoadhesive strength, ex vivo mucoadhesion time, in vitro drug release, and in vitro drug permeation. As compared with bilayered tablets, multilayered tablets showed slow release rate of drug with improved ex vivo bioadhesive strength and enhanced ex vivo mucoadhesion time. The mechanism of drug release was found to be non-Fickian diffusion (value of n between 0.5 and 1.0) for both the buccal devices. The stability of drug in both the optimized buccal devices was tested for 6 hours in natural human saliva; both the buccal devices were found to be stable in natural human saliva. The present study concludes that mucoadhesive buccal devices of PRH can be a good way to bypass the extensive hepatic first-pass metabolism and to improve the bioavailability of PRH.

Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride.

Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride Mucoadhesive buccal patches containing propranolol hydrochloride were prepared using the solvent casting method. Chitosan was used as bioadhesive polymer and different ratios of chitosan to PVP K-30 were used. The patches were evaluated for their physical characteristics like mass variation, drug content uniformity, folding endurance, ex vivo mucoadhesion strength, ex vivo mucoadhesion time, surface pH, in vitro drug release, and in vitro buccal permeation study. Patches exhibited controlled release for a period of 7 h. The mechanism of drug release was found to be non-Fickian diffusion and followed the first-order kinetics. Incorporation of PVP K-30 generally enhanced the release rate. Swelling index was proportional to the concentration of PVP K-30. Optimized patches (F4) showed satisfactory bioadhesive strength of 9.6 ± 2.0 g, and ex vivo mucoadhesion time of 272 minutes. The surface pH of all patches was between 5.7 and 6.3 and hence patches should not cause irritation in the buccal cavity. Patches containing 10 mg of drug had higher bioadhesive strength with sustained drug release as compared to patches containing 20 mg of drug. Good correlation was observed between the in vitro drug release and in vitro drug permeation with a correlation coefficient of 0.9364. Stability study of optimized patches was done in human saliva and it was found that both drug and buccal patches were stable.

Mucoadhesive bilayer tablets of propranolol hydrochloride.

The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets containing Na-alginate and CP in the ratio of 5∶1 (F2) had the maximum percentage of in vitro drug release without disinte-gration in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface pH of all tablets was found to be satis-factory (7.0±1.5), close to neutral pH; hence, buccal cavity irritation should not occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics. The formulation F4 was optimized based on good biodhesive strength (28.9±0.99 g) and sustained in vitro drug permeation (68.65%±3.69% for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration.

Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique

The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4). Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.

Once-Daily Sustained-Release Matrix Tablets of Losartan potassium: Formulation and In Vitro Evaluation

Objective of the present study was to develop hydrophilic polymer and hydrophobic polymer based matrix Losartan potassium sustained release tablet which can release the drug up to time of 24 hrs in predetermined rate. Formulation of Losartan potassium matrix tablet was prepared by the polymer combination in order to get required theoretical release profile. Influence of hydrophilic and hydrophobic polymer on Losartan potassium was studied. Formulated tablet were also characterized by physical and chemical parameters. In vitro release profile was check for 24 hrs to evaluate the SR matrix tablet of Losartan potassium. Losartan potassium (LP) is a potent, highly specific Angiotensin II type 1 (AT1) receptor antagonist with antihypertensive activity. It is readily absorbed from the gastrointestinal tract with oral bioavailability of about 33% and a plasma elimination half-life ranging from 1.5 to 2.5 hr. Administration of LP in a sustained release dosage would be more desirable for anti- hypertensive effects by maintaining the plasma concentrations of the drug well above the therapeutic concentration. From in vitro dissolution profile, Batch B4 was prepared with blend of HPMC K4M (67.2 mg), HPMC K200M(90mg) and Eudragit RSPO(112.5 mg), where drug release was about 94-98%. Batch B4 showed highest similarity factor values (f 2 = 67.76). KEYWORDS: Losartan potassium, HPMC K4M, HPMC K200M, Eudragit RSPO, Sustained release, Matrix tablets.

“Mas Spec Pen”, The New Future For Cancer Diagnosis: Mini Review

On 6th September 2017, Jialing Zihang an assistant professor, department of Chemistry, University of Texas at Austin and his center-dedicated team published a revolutionized work in science translational medicine research journal [1]. Their work could entirely eradicate cancer from its grass root. The research was comprised of performing a non-destructive tissue analysis in out of the body and diagnose of carcinoma within the living cells using a “MasSpec Pen”. This “MasSpec Pen” is actually a probe, which is connected to a Mass spectrometer (Figure 1). Modern oncologists and scientist are always facing tremendous challenging’s in tissues assessment and diagnosis in cancer treatment because of screening cancerous cells from normal cells. Many women diagnosed with breast cancer would undergo conserving surgery. This means the cancer surgeon has to face challenges to separate cancerous cells from within normal cells to maintain a total integrity of the mammary gland. In similar fashion, in lung cancer, complete resection of a primary tumor is the prerequisite because after surgery it was often witnessed the residual cancerous cells progress retrievable. Likewise, in ovarian cancer, the residual carcinoma cells could generate negative responses to chemotherapeutic treatment. Thus, it has become necessary to estimate negative margin assessment and excision of a complete tumour. Moreover, interpretations of the cancer cell are a tedious process, it is a big concerned for any histopathologist to detect ontogenesis using normal frozen section method and with intraoperative frozen section method because of its time consumptions, interactions of freezing arti-facts with tissue morphology and patient life risk due to extended anaesthesia. If positive marginal oncogenic cellswere found, the patients were subjected to additional surgery, hyperactive anxiety and discomfort [2-5]. There for it is becoming an indispensable need to analysis oncogenes in molecular labels by incorporating cancer specific biomarkers to improve cancer identification and screening. At present era, distinguished ex-vivo and in–vivo tests are available using molecular imaging technology, which has very effective implications in pre-clinical and clinical studies. Some other effective techniques in cancer diagnosis are targeting biomarkers, genes sequencing technology, fluorescence probes targeting tumor cells, stimulated Raman scattering microscopy and spectroscopy, and Mass spectrometry that is used to detect molecular imaging of cancerous tissues. Abstract

Formulation and Evaluation of Aciclovir Loaded Novel Gelfor Topical Application

Herpes simplex virus (HSV) is a double-stranded, enveloped, DNA virus. Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) belong to the family Herpesviridae, subfamily Alpha herpesvirinae. Following initial infection, the herpes viruses become latent in the sensory neural ganglia (the trigeminal ganglion in HSV-1 infection [1] and the sacral ganglion in HSV-2 infection).ACV mainly used for the first line treatment of herpes virus infection., and varicellazoster virus (VZV).The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. ACV has low oral bioavailability of 1020%. ACV administered by the oral, topical, & intravenous route in herpes infection [2] When administrated orally often results in general side effects, including Anaphylaxis, angioedema, fever, headache, pain, peripheral edema, gastrointestinal disturbances likes diarrhoea, nausea [3]. Topical administration of ACV (cream or ointment) has side effects like flakiness of the skin, burning or stinging feeling, or itching of skin [4]. Controlled drug delivery by topical administration produce steady-state phenomenon which is ultimately reduced systemic side effect and provide improved efficacy as compared to other dosage forms. Main disadvantage of Acyclovir is that it is poor water solubility and it is insoluble in hydrophobic solvents. So, it is not possible to produce a topical formulation which having sufficient concentration of active ingredient to produce its desired therapeutic effect and it is also difficult to optimize flux of the formulation through the skin. In case of rate of release of drug, it is also significant that any dosage form of a therapeutically active ingredient; should be stable for longer period; its potency should be retain; should not produce any colour change or produce insoluble ingredient and should also non irritating to the mucosa [5].

A Comprehensive Updates on Zika Virus

Most Aedes mosquitoes are responsible for Zika virus infected disease. Most people are suffering from Zika virus which persist skin rashes, mild fever, conjunctivitis, joint and muscle pain and other peripheral complications. Eventually, these symptoms predominance last for two to seven days. Avoiding mosquito’s bites are the best possible way to avoid this infection. The virus shows it bitter tooth on partial tropical parts of the Americas, Africa, Pacific, tropical parts of Asia. Indian vaccine company, Bharat Biotech makes us proud by developing world first Zika vaccine ZIKAVAC©.

Bioavailability enhancement study of BCS class IV drug: Snedds approach

T aim of current study entails to develop a solid lipid nanoparticle (SLN) as a novel lipid nanocarrier for the oral delivery of decitabine (DCB) using cold homogenization technique. A Box-Behnken design (33) with 17 experimental runs was constructed to identify the key independent variables influencing on dependent variables. The optimized batch (SLN-11) was further characterized with particle size distribution, zeta potential, TEM, entrapment efficiency, drug content, rheological study, DSC, in vitro drug release, and accelerated stability. The optimized batch revealed spherical morphology under TEM analysis with particle size of 136.6± 2.35 nm and 0.244±0.002 PDI. Zeta potential and %EE was found to be -31.34±0.67 mV and 58.89% ±0.78 respectively. In vitro release studies showed burst release at the initial stage followed by sustained release up to 24 hrs in intestinal medium and the data was further studies using release kinetic models which revealed Higuchi matrix as a best fitted model. Finally, SLN prepared using Precirol ATO5 as solid lipid and surfactants as Poloxamer 188, Tween 80 and Solutol HS15 (2:1:2 ratio) posses high potential to entrap DCB in lipid nanoparticle, showed better prospects for the oral delivery of DCB.C (cur), a natural compound elicit a spectrum of potent responses both locally and systemically. However its local effect in buccal conditions is largely hindered by its extremely limited water solubility, and its hydrolytic degradation in salivary pH. The aim of the present study was to develop buccal mucoadhesive tablets of cur with accepted release and stability at salivary pH as well as to design a simple in vitro dissolution test ensuring its stability. Chemical stability in phosphate buffer saline (PBS) pH 6.8 was tested using a group of stabilizers of which sodium lauryl sulfate (SLS) proved to be the most suitable. Different muccoadhesive tablets formulations were prepared by direct compression technique using a mixture of Hydroxypropyl methylcellulose (HPMC) K15M and Carboxymethylcelluose sodium (NaCMC) in different ratios with or without SLS as stabilizer, curas pure untreated drug or in the form of rapidly dissolving solid dispersion (SD) with PVP (Kollidon®25). Formulations were evaluatedfor mucoadhesive strength, in vivo and in vitro residence time, release studies and clinical evaluation of the selected formulation. The best mucoadhesive performance and in vitro sustained release profile (70% released over 12 hours) were exhibited by tablets containing HPMC.K15M: CMC sodium (5:1), SD (1:3) with 15 mg SLS. Salivary concentration (conc.) was significantly increased compared to undetectable conc. for pure cur due to poor solubility and SD without SLS due to hydrolytic degradation. Preliminary clinical study revealed an excellent anti-inflammatory and healing effect. Cur in this delivery system is an excellent candidate for local buccal delivery.T purpose of present study is to formulate SNEDDS of BCS Class-IV (Exemestane HCl) to investigate its potential oral drug delivery system by improving its bioavailability. Preformulation study was done for selection of oils, surfactants & co-surfactants. Based on the solubility studies, Caprol microexpress and Labrafac as oil phase, Tween 80 as a surfactant and Triacetin as a co-surfactant were selected. Phase studies were performed using different ratio like (1:1, 1:2, 1:3, 2:1, 3:1) [oil: (surfactant/co-surfactant)]. Pseudo ternary phase diagram were prepared, Tween 80: triacetin (1:2) and (1:3) ratio showed the highest area for the preparation for the nanoemulsion. All formulations were evaluated for the visual assessment, optical clarity, particle size, drug content, viscosity, in vitro release study. From vitro characterization results, three formulations were selected as potential formulation for in vitro cytotoxicity screening and in vivo pharmacokinetic study. EX1 showed particle size (29.56 nm), Polydispersity index (0.523), Zeta potential (-40.3), & drug release after 120 min. was 99.589±1.85 % EX2 showed particle size (37.65 nm ), Polydispersity index (0.835), Zeta potential (-30.3), & drug release after 120 min was 99.17±1.81 % EX3 showed particle size (44.73 nm), Polydispersity index (0.679), Zeta potential (-15.7), & drug release after 120 min was 98.172±1.29 % due to its low particle size and excellent stability. The dose response curves demonstrated that Exemestane SNEDDS had less cytotoxicity compared to the drug solution alone after 24 hrs but EX2 showed greater % cell inhibition as well as greater AUC Compare to EX3 and EX1. It can be concluded that SNEDDS is a novel and commercially feasible approach to improve oral bioavailability of BCS class-IV drug like exemestane HCL.T aim of present study was the development of hyaluronic acid (HA)-targeted pH-sensitive liposomes (SL-pH-HA) for intracellular delivery of doxorubicin (DOX) in the cancer cell that express CD44. The in vitro release studies demonstrated that the release of DOX from SL-pH-HA was pH-dependent, i.e., faster at mildly acidic pH ~5, compared to physiological pH ~7.4. SL-pH-HA was evaluated for cytotoxicity potential on MCF-7 cells. The quantitative uptake study by flow cytometry revealed higher localization of targeted liposomes in the receptor positive cells, which was further confirmed by fluorescent microscopy. The in vivo antitumor activity in tumor bearing mice was also confirmed the efficacy of HA targeted pH-sensitive liposomes. The major side-effect of DOX i.e., cardiotoxicity was also estimated by measuring serum enzyme level. Thus, HA targeted pH-sensitive liposomes were significantly more potent than the non-targeted liposomes in cells expressing high levels of CD44, which suggests that they may be a useful targeted drug carrier to treat CD44-expressing breast tumors.Introduction: Warfarin is the most widely used anticoagulant in the world. The difficulty of managing warfarin contributes to great potential for patient harm, both from excessive anticoagulation and insufficient anticoagulation. Objective: To assess the INR control outcome measures for warfarin therapy, to investigate quality of warfarin prescribing and to assess level of patients’ knowledge on warfarin therapy among outpatients in Tikur Anbessa Specialized Hospital (TASH). Methodology: The study was based on cross sectional study design involving retrospective chart review and Oral Anticoagulation Knowledge Assessment (OAKA) questionnaires. 360 patients’ charts were included and 130 patients were interviewed in this study. Result: Patients spent 52.2%, 29% and 18.8% of the times in subtherapeutic, therapeutic and supratherapeutic ranges, respectively. The daily warfarin dose was increased in (50.9% and 36.9%) and decreased in (52.8% and 60.9%) of the times for occurrences of subtherapeutic and supratherapeutic International Normalized Ratio (INRs) to achieve target ranges of 2.0-3.0 and 2.5-3.5 respectively. The majority of patients (76.9%) had moderate knowledge on warfarin therapy. The mean score of patients on correct response was 11.8±2.5 (59.3%± 12.8%). Among interviewed patients only 13.9% of them got passing scores. Conclusion and Recommendation: This study found that quality of anticoagulation management with warfarin among outpatients in TASH was suboptimal. This was reflected by low Time in Therapeutic Range, longer INR monitoring frequency, minimal actions taken to adjust warfarin dose after occurrences of nontherapeutic INRs; and poor patients’ knowledge. Establishing pharmacist managed anticoagulation clinic which supported by computer software programs may be the integral part of anticoagulation management services in TASH.Materials and Methods: Nanoarticles were prepared in two steps. Firstly biodegradable amphiphilic polymer i.e., poly (H2NPEGCA-co-HDCA) was synthesized which is having high encapsulation efficiency. In second step, doxorubicin and peptide encapsulated NPs of synthesized polymer was prepared using double emulsification method reported by Stella (2000) which was further conjugated with transferrin as reported by Minghuang (2010). The optimized NPs formulations such as NpfDox, Npf-Dox-Tf, Npf-Dox-Tf-Ga respectively were used for further studies. Size and size distribution of NPs were determined using a Zetasizer (Malvern Instruments, UK). Shape and surface morphology of NPs were studied using TEM and SEM. In vitro drug release was carried using dialysis bag (MW 1200 da). Ex vivo antitumor studies such as MTT cell cytotoxicity and cell uptake study were carried out on MCF-7 human breast cancer cell line.HE POSSIBLE anti-inflammatory, cytotoxic and hepatoprotective activities of Laurus nobilis L. wood extract was in vitro evaluated. The anti-inflammatory activity was assessed by measuring Nitric Oxide (NO) production by the inflammagen lipopolysacchride. The extract was evaluated for its cytotoxic activity on six different human cancer cell lines together with the normal non-malignant melanocytes cell line (HFB4) using the SRB assay. The hepatoprotective activity against paracetamol toxicity was determined using primary cultured rat hepatocytes. The extract showed moderate anti-inflammatory activity as shown in the amount of nitric oxide produced with a level of 4.3 μM /ml (67 % inhibition), in comparison to the potent anti-inflammatory drug Dexamethasone (95 % inhibition). The extract was found to have moderate cytotoxic activity against the tumor cell lines used at the applied concentrations with IC50 ranging from 15.5 – 47.6 μg/ml compared to the potent cytotoxic drug doxorubicin. The wood extract showed hepatoprotective activity against paracetamol toxic effect at concentration of 20g/ ml. The constitutive phenolics of L. nobilis L. wood were studied and led to the separation and identification of 12 compounds, all isolated for the first time from L. nobilis L. wood and were identified using chemical, conventional and advanced spectral techniques.An oral press-coated tablet was prepared by using direct compression and wet granulation methods to achieve the predetermined lag time. This press-coated tablet containing montelukast sodium in the inner core was formulated with an outer barrier layer by different compositions of hydrophobic polymer ethylcellulose and hydrophilic polymer low-substituted hydroxypropylcellulose. The effect of formulation composition on the barrier layer comprising both hydrophobic and hydrophilic excipients on the lag time of drug release was investigated. It was observed that lag time decreases with increasing concentration of low-substituted hydroxypropylcellulose. Press coated tablets coated by dry mixing and by wet granulation showed variations in lag time. As compared to dry mixed blend method wet granulation method gives less lag time.Oral salbutamol sulphate has site-specific absorption in the stomach and upper part of the small intestine. Its bioavailability is about 40% due to several factors including narrow absorption window and extensive intestinal metabolism. The aim of this study was to formulate and optimize sustained release floating tablets of salbutamol sulphate in order to improve its bioavailability and reduce its dosing frequency. Accordingly, floating tablets were prepared by wet granulation technique and drug release analysis was performed by HPLC. The effects of polymer level, polymer type (XG or HPMC), polymer ratio (XG/HPMC; 1:1, 1:3, 3:1) and NaHCO3 level on floating lag time, floating duration, cumulative release within 1 hr, and release rate were investigated. From preliminary studies, the polymer with 1:3 (XG:HPMC) ratio and NaHCO3 were selected as significant factors and cumulative release at 1 hr and release rate were chosen as significant responses, respectively. Hence, the effect of these factors were further studied and optimized by central composite design. The most desirable representative optimal point was obtained at 24.79% of XG/HPMC and 5% of NaHCO3 having release rate of 28.49 hr -1/2 and cumulative release at 1 hr of 24%. This formulation is expected to significantly improve bioavailability of salbutamol while remaining buoyant and sustained release INTRODUCTION: Salbutamol sulphate is one of the widely used drugs in the treatment of respiratory disorders like bronchial asthma, chronic bronchitis and obstructive airway diseases 1 . The relatively short acting injectable and aerosol dosage forms of salbutamol sulphate are recommended for instant relief in severe asthmatic attacks. QUICK RESPONSE CODE DOI: 10.13040/IJPSR.0975-8232.6(5).1877-92 Article can be accessed online on: www.ijpsr.com DOI link: http://dx.doi.org/10.13040/IJPSR.0975-8232.6(5).1877-92 The recommended dose of aerosols in adults and children is 2 – 3 inhalations every 4 – 6 hr 2 and for conventional tablets, 2-6 mg (base) is administered three to four times a day 3 which causes poor patient compliance, multiple administration associated side effects, and plasma drug level fluctuation. Salbutamol sulphate has oral bioavailability of only ~40% due to extensive metabolism via intestinal sulphonation, first pass metabolism in the liver, narrow absorption window (site-specific absorption in stomach and upper part of small intestine 4 and degradation in colon 5, 6 . Hence, development of