Papers by Aliasgar Shahiwala
Advancements in bioequivalence & bioavailability, Mar 26, 2018
In drug development process, the formulation of drug and its bioavailability are the major concer... more In drug development process, the formulation of drug and its bioavailability are the major concerns in getting approval to conduct clinical trials. A poor bioavailability and solubility property of a product leads to rejection and fail to reach the market. Poor bioavailability of drugs is due to various factors for example aqueous solubility, drug permeability, dissolution rate, first-pass metabolism, etc. [1]. The most leading factor of poor bioavailability is the low solubility and permeability. Therefore, there are extensive researches to study the Biopharmaceutics Classification System (BCS) class II, III and IV and to develop new technologies to overcome the problem of poor solubility and/or permeability. Alteration in drug delivery process may produce substantial changes in bioavailability and solubility of a drug. There are array of cutting edge techniques which are developed and have been used by some pharmaceutical companies to enhance the solubility and improve bioavailability. Identifying the need of appropriate technologies at the earlier stages of drug discovery may increase the chances of overall success rate of approval which in fact saves unnecessary expenditure and reduce the cost of drug development. The degree of solubility of a drug in a definite solvent is measured as the saturation concentration where adding more solute does not increase its concentration in the solution [2]. Different pharmacopoeias have defined solubility regardless of solvent used, in terms of quantification and defined the criteria as given in Table 1 [3].
Therapeutic Delivery, Oct 1, 2019
Colorectal cancer (CRC) is considered the third most frequent malignant neoplasm occurring in 5 b... more Colorectal cancer (CRC) is considered the third most frequent malignant neoplasm occurring in 5 both men and women worldwide. Most approaches that have been used to fight and treat this 6 type of malignancy are either invasive or non-selective. Non-invasive therapy using oral route 7 can increase patient compliance and reduce treatment costs. Innovative measures such as use of 8 nanotechnology and theranostic systems have been initiated in the oral therapy, which has been 9 proven to be greatly advantageous in decreasing side effects, improving detection and diagnoses. 10 This manuscript investigates recent innovative and novel therapeutic approaches through oral 11 route and potential targets in the treatment of CRC.
Novel approaches in drug designing & development, 2020
Drug design development and delivery journal, Oct 21, 2019
Copyright: © 2019 AlAteib NA, et al. This is an open-access article distributed under the terms o... more Copyright: © 2019 AlAteib NA, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 international License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Vium mor li, poracidisus es condam Introduction Pediatrics and elderly patients specifically; are difficult to control while administering the unpleasant taste of specific drug, leading to administer fewer doses, which cause less efficiency. Taste masking is the proper way to improve the quality of the treatment [1]. The taste masking defined as a perceived decrease of an unpleasant taste of active pharmaceutical ingredients [2]. There are several applications and methodologies of taste masking, and each method has specific advantages. The easiest method involves the use of flavor enhancers and in case no results found with this method, then complex methodologies comes on the board. The techniques found to be effective on taste masking are; inclusion complex formation with cyclodextrin, ion exchange resins, granulation, liposome, microencapsulation, multiple emulsions, prodrug approach, polymer coating, solubility limiting methods, and the use of anesthetic agents [3]. Then evaluation of the taste masking is essential, such as evaluation of liquid and solid dosage forms, evaluation of microspheres, recent innovations, recent trends (AdvaTab ODT Technology), recent trends (Microcaps ODT Technology), liquitard ODT Technology, for multiplex and formulcoat, and linecaps. Moreover, a recent innovation tastes masking by using electronic tongue.
Springer eBooks, 2019
Repositioning an old drug through intraoral drug delivery system benefits the pharmaceutical manu... more Repositioning an old drug through intraoral drug delivery system benefits the pharmaceutical manufacturer by imparting unique product differentiation and enabling its use as line extensions for existing commercial products. Although the needs for these systems are real, and many classes of drugs could benefit from intraoral drug delivery, turbulent and changing nature of the oral cavity, less surface area, and contact time pose significant formulation challenges. This chapter discusses all these challenges and different approaches that can be adopted in formulating an intraoral dosage form. This chapter further provides details of approved marketed products, products that have recently completed or in ongoing clinical trials, and regulatory requirements for bioequivalence for intraoral dosage forms.
Journal of Drug Delivery Science and Technology, Feb 1, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Journal of Drug Targeting, 2008
The objective of this study was to develop and evaluate squalane oil-containing water-in-oil-in-w... more The objective of this study was to develop and evaluate squalane oil-containing water-in-oil-in-water (W/O/W) multiple emulsion for mucosal administration of ovalbumin (OVA) as a model candidate vaccine in BALB/c mice. Control and optimized OVA-containing W/O/W emulsion (OVA-Emul) and chitosan-modified W/O/W emulsion (OVA-Emul-Chi) formulations were administered intranasally and orally at an OVA dose of 100 mug. The mucosal and systemic immune responses were evaluated after the first and second immunization. The OVA-Emul formulations resulted in higher immunoglobulin-G (IgG) and immunoglobulin-A (IgA) responses as compared with aqueous solution. In addition, significant IgG and IgA responses were observed after the second immunization dose using the emulsions with both routes of administration. Intranasal vaccination was more effective in generating the systemic OVA-specific IgG response than the mucosal OVA-specific IgA response. Oral immunizations, on the other hand, showed a much higher systemic IgG and mucosal IgA responses as compared with the nasally treated groups. The results of this study show that squalane oil-containing W/O/W multiple emulsion formulations can significantly enhance the local and systemic immune responses, especially after oral administration, and may be adopted as a better alternative in mucosal delivery of prophylactic and therapeutic vaccines.
Current Drug Targets, Apr 1, 2023
: Breast cancer has remained a global challenge and the second leading cause of cancer mortality ... more : Breast cancer has remained a global challenge and the second leading cause of cancer mortality in women and family history. Hereditary factors are some of the major risk factors associated with breast cancer. Out of total breast cancer cases, 5-10% account only for familial breast cancer, and nearly 50% of all hereditary breast cancer are due to BRCA1/BRCA2 germline mutations. BRCA1/2 mutations play an important role not only in determining the clinical prognosis of breast cancer but also in the survival curves. Since this risk factor is known, a significant amount of the healthcare burden can be reduced by taking preventive measures among people with a known history of familial breast cancer. There is increasing evidence that phytochemicals of nutrients and supplements help in the prevention and cure of BRCA-related cancers by different mechanisms such as limiting DNA damage, altering estrogen metabolism, or upregulating expression of the normal BRCA allele, and ultimately enhancing DNA repair. This manuscript reviews different approaches used to identify potential phytochemicals to mitigate the risk of familial breast cancer with BRCA mutations. The findings of this review can be extended for the prevention and cure of any BRCAmutated cancer after proper experimental and clinical validation of the data.
Drug delivery letters, Sep 1, 2023
Background: This study aims to assess the suitability of in vitro drug release methods, dialysis ... more Background: This study aims to assess the suitability of in vitro drug release methods, dialysis and paddle methods for predicting in vivo behaviour of Aceclofenac (ACE) proniosomes. Methods: ACE proniosomes are prepared using different carriers: glucose, maltodextrin and manni-tol by the slurry method. The release studies of ACE proniosomes formulations were performed us-ing the paddle, and dialysis methods while in vivo studies were performed in albino rats. Graphical presentation, model-dependent and model-independent approaches were applied to compare two dissolution methods. Results: More than 70% of the drug was released from ACE proniosomes over 60 min by paddle method while not more than 5% was released in the same period by dialysis method. The paddle method provides a reproducible and faster release, whereas poor drug release occurred with the di-alysis method. For the paddle method, lower values of similarity factor (f2) and greater differences in the dissolution efficiency (DE) amongst different formulations and in comparison, to that of the pure drug indicates that it is a more discriminative method compared to dialysis. The paddle method also illustrated high regression coefficients (r2) of 0.81, 0.998 and 0.975 for FN1, FN2, and FN3, respectively for level A IVIVC, while poor or no relation (r2 < 0.1) was detected in the case of dialy-sis method. Conclusion: Based on the results, the paddle method is concluded to be the more suitable method compared to the dialysis method for in vitro drug release studies of a novel dosage form such as proniosomes.
Current Drug Delivery, Oct 1, 2009
Fertility and Sterility, Mar 1, 2004
Objective: To ascertain the nasal bioavailability of Levonorgestrel and change formulation compon... more Objective: To ascertain the nasal bioavailability of Levonorgestrel and change formulation components to provide long-term effective concentrations of the drug in blood. An experimental study was conducted on rats to reduce dose and/or frequency of drug administration to reduce expected side effects reported in humans. Design: In vivo study in rats.
Journal of Pharmacy and Pharmacology, 2006
The purpose of the study was to investigate the nasal route as a non-invasive alternative for del... more The purpose of the study was to investigate the nasal route as a non-invasive alternative for delivery of leuprorelin acetate (leuprolide acetate, LEU) and to achieve an effective concentration of leuprorelin acetate in blood after nasal administration for contraception in rats. The plain drug solution, physical mixture (plain drug along with constituents of liposomes), or drug encapsulated in Although there are currently no systemic methods of contraception for use by men, the development of male-use contraception equivalent to oral, injectable and implantable female steroid hormone methods of contraception has been the subject of research for the past 30 years or more. A number of studies in animals and man have shown that the administration of androgens alone, androgen and progestin combinations, and combinations of
Aaps Pharmscitech, Sep 1, 2005
PubMed, Jan 30, 2003
Purpose: A niosome based transdermal drug delivery system of Nimesulide (NIM) was developed and e... more Purpose: A niosome based transdermal drug delivery system of Nimesulide (NIM) was developed and extensively characterized and evaluated for in-vitro performance followed by in-vivo evaluation in rats by carrageenan induced rat paw edema method. Method: Niosomes were prepared by lipid film hydration technique using tweens and spans. Preparation of niosomes was optimized for highest percent drug entrapment (PDE). The prepared niosomes were incorporated into 1 percent carbopol gel base and the system was evaluated for drug diffusion across human cadaver skin (HCS) using modified validated diffusion cell. The drug retention studies in niosomes were performed at refrigerated temperature (2 degrees C - 8 degrees C) and at room temperature (25 degrees C+/-2 degrees C) for the period of 2 months. In-vivo performance of plain drug gel, niosomally-entrapped drug in carbopol gel base and marketed formulation were evaluated using acute rat paw edema method. Results: Highest mean percentage edema inhibition (PEI) was observed for niosomal nimesulide gel after 24 hours i.e. 66.68 percent +/- 5.19 percent compared to plain drug gel i.e. 12.57 percent +/- 1.78 percent and marketed NIM formulation i.e. 20.49 percent +/- 0.91 percent. Conclusion: Findings of this investigation conclusively demonstrate prolongation of drug release and increase in amount of drug retention into the skin and permeation across the skin after niosomal encapsulation of NIM. Developed nimesulide niosomal gel formulation has also demonstrated enhanced anti-inflammatory activity compared to plain drug gel and marketed formulation.
Journal of Receptors and Signal Transduction, Jan 2, 2020
Colorectal cancer (CRC) is the third most common malignancy among both the genders globally. Ther... more Colorectal cancer (CRC) is the third most common malignancy among both the genders globally. Therefore, searching of new therapeutic options is utmost priority. Molecular docking is a widely used tool in drug discovery to identify potential new therapeutic targets. Molecular docking plays a vital role in the visualization of ligand-protein interaction at an atomic level and enhancing our understanding of the ligand behavior thus aiding in the structure-based drug designing. Selected phytochemicals with potential anticancer activities were examined for their binding affinities to the selected VEGFR and EGFR receptors. The receptor protein 3D structures were obtained from Protein Data Bank, and the molecular docking was performed using UCSF Chimera software with its AutoDock Vina tool. Out of 18 compounds screened, Yuanhuanin, Theaflavin, and Genistein have shown highest binding energies. Findings of this study should be further evaluated for their potential use in CRC treatment, management, and prevention.
Expert Opinion on Drug Delivery, Oct 13, 2011
Disease management of outdoor patients is mainly affected by patient compliance to the drug thera... more Disease management of outdoor patients is mainly affected by patient compliance to the drug therapy, which in turn is governed by patient convenience. Failure to follow through with a treatment decision is one of the biggest causes of unsuccessful medical care. At present, different formulation options are available for various drugs, and hence, the decision is based on the most convenient dosage form for the patient, along with optimum therapeutic benefits. This paper reviews various available formulation approaches, in the hope of improving patient convenience, compliance and the overall outcome of oral drug therapy. While parenterals are valued for their speed and efficiency of delivery, these systems generally score low on patient satisfaction surveys. The oral route is the preferred route for drug delivery, although it renders multiple obstacles to formulate a patient-convenient platform, such as unfavorable taste and swallowing difficulties. Transdermal drug delivery also provides high patient satisfaction, but is effective only for the delivery of smaller, lipophilic molecules. The increasing development of biopharmaceutical therapies renders an increasing number of challenges for formulation scientists to develop a more patient-convenient means of drug delivery.
Journal of Controlled Release, Mar 1, 2009
In the body under physiological conditions, many vital functions are regulated by transient relea... more In the body under physiological conditions, many vital functions are regulated by transient release of bioactive substances at a specific time and site. Thus, to mimic the function of living systems and in view of emerging chronotherapeutic approaches, pulsatile delivery, which is meant to release a drug following programmed lag phase, has attracted increasing interest in recent years. In pursuit of pulsatile release, various design strategies have been proposed, broadly categorized into single-unit and multiple-unit systems. However, in recent pharmaceutical applications involving pulsatile delivery, multiparticulate dosage forms are gaining much favor over single-unit dosage forms because of their potential benefits like predictable gastric emptying, no risk of dose dumping, flexible release patterns and increased bioavailability with less inter-and intra-subject variability. Based on these premises, the aim of the present review is to survey the main multiparticulate pulsatile delivery systems, for which the swelling and rupturing; dissolution or erosion; and changed permeability of the coating membrane are primarily involved in the control of release. The development of low density floating multiparticulate pulsed-release dosage forms possessing gastric retention capabilities has also been addressed with increasing focus on the upcoming multiparticulate-pulsatile technologies being exploited on an industrial scale.
Springer eBooks, 2019
The present research has been undertaken with the aim to develop a topical gel formulation of dic... more The present research has been undertaken with the aim to develop a topical gel formulation of diclofenac sodium using a micronized fumed silicon dioxide (Aerosil) gelled with a liquid paraffin (non-polar vehicle). The two gels, 8% (formulation A) and 10% (formulation B) were prepared from hydrophilic colloidal silicon dioxide (Aerosil 200) and their physicochemical characterization and efficacy as oleaginous ointment bases were investigated. They were evaluated for physicochemical properties such as homogeneity, grittiness, viscosity, pH, spreadability, drug content, skin irritancy, in vitro drug and ex vivo drug release. Compatibility studies were carried out using FT-IR spectroscopy. Developed gels were found to be comparable to marketed products in all physicochemical aspects tested. No significant changes in the peak pattern of IR spectra of pure diclofenac sodium implies that no chemical incompatibility between drug and excipients used in the formulations. Drug permeation through the rat abdominal skin membrane was slow as compared to the synthetic membrane for all the formulations tested. Permeation data for all the tested formulations were found to follow zero-order kinetics with Fickian diffusion mechanism, indicating that drug permeations were independent of the drug concentrations in the gels. The prepared gels showed significant analgesic activity in rats as compared to the control value. Also, the application of gels showed no skin irritation throughout the entire observation period. Based on the results of this investigation, formulation A with 8% aerosil gel base in liquid paraffin was found to be a promising formulation for further clinical investigations.
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Papers by Aliasgar Shahiwala