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saudi journal of medical and pharmaceutical sciences abbreviated key title saudi j med pharm sci issn 2413 4929 print issn 2413 4910 online scholars middle east publishers dubai united arab ...

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                                                                                                                    Saudi Journal of Medical and Pharmaceutical Sciences 
                                                                                                                                                                              Abbreviated Key Title: Saudi J Med Pharm Sci  
                                                                                                                                                                         ISSN 2413-4929 (Print) |ISSN 2413-4910 (Online) 
                                                                                                                                                        Scholars Middle East Publishers, Dubai, United Arab Emirates 
                                                                                                                                                                                  Journal homepage: https://saudijournals.com  
                                                                                                                                                                                                                                                   
                                                                                                                                                                                                               Review Article 
                         
                        Artificial  Neural  Networks  in  Optimization  of  Pharmaceutical 
                        Formulations 
                                                                  1                                                     1                                      2                                    3                                      1*
                        Manoj Kumar Ananthu , Pavan Kumar Chintamaneni , Shakir Basha Shaik , Reshma Thadipatri , Nawaz Mahammed  
                          
                        1Department  of  Pharmaceutics,  Raghavendra  Institute  of  Pharmaceutical  Education  and  Research  (RIPER)-Autonomous, 
                        Ananthapuramu, Andhra Pradesh, India 
                        2Department of Pharmaceutical Analysis, Raghavendra Institute of Pharmaceutical Education and Research (RIPER)-Autonomous, 
                        Ananthapuramu, Andhra Pradesh, India 
                        3Department  of  Pharmaceutical  Quality  Assurance,  Raghavendra  Institute  of  Pharmaceutical  Education  and  Research  (RIPER)-
                        Autonomous, Ananthapuramu, Andhra Pradesh, India 
                         
                        DOI: 10.36348/sjmps.2021.v07i08.004                                                                 | Received: 17.07.2021 | Accepted: 20.08.2021 | Published: 24.08.2021 
                         
                        *Corresponding author: Nawaz Mahammed 
                         
                          Abstract                              
                         
                        Artificial Neural Network is a Computer program Based on simulation of Neurons of human brain. During the past Statistical Methods 
                        like RSM (Response Surface Methodology). Other statistical methods are used for the development of Modified release formulations 
                        (Controlled Release & Sustained Release formulations). Due to draw backs of statistical methods another technique is Artificial Neural 
                        Network. ANN has an emerging field in the Development of Modified release formulations (CR & SR). This review article containing 
                        the optimized formulations of different modified release formulations by ANN and also Structure of Artificial Neural Network (ANN), 
                        different optimized formulations are developed by using ANN are discussed. ANN helps in emerging field in the optimization of 
                        pharmaceutical formulations. ANN are learning according to the different set of data given to the neural networks. The functioning of 
                        the Artificial Neural Network identified according to the given output data of the formulations. ANN is a very powerful tool in the 
                        Pharmaceutical industries, Academics, Research institutes to develop new formulations. 
                        GRAPHICAL ABSTRACT 
                                                                                                                                                                                                                                    
                        Keywords:  Artificial  neural  network,  Modified  release  formulations,  Controlled  Release  &  Sustained  Release 
                        formulations, Computer, Response surface Methodology, Network architecture. 
                        Copyright © 2021 The Author(s): This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International 
                        License (CC BY-NC 4.0) which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original 
                        author and source are credited. 
                                                                                                                                                                                                                                           
                         Citation:  Manoj  Kumar  Ananthu  et  al  (2021).  Artificial  Neural  Networks  in  Optimization  of  Pharmaceutical                                                                                             368 
                         Formulations. Saudi J Med Pharm Sci, 7(8): 368-378. 
                         
                         
                                                                                                                                                
                                                                                                                                                
                                                                   Manoj Kumar Ananthu et al., Saudi J Med Pharm Sci, Aug, 2021; 7(8): 368-378 
               1.  INTRODUCTION                                                              Artificial neural networks (ANN) are computer 
                        Pharmaceutical  formulations  are  dynamic                  systems    programmed  to  use  multiple  learning 
               structures in which various formulation and technique                algorithms to replicate the functions of the human brain, 
               variables  it  might  not  be  that  readily  understanding          that  can  be  learn  from  experience.  Topological-
               impact. the properties and performance characteristics.              dependent feed-forward and feed-back may be the link 
               Pharmaceutical  optimization  is  characterised  as  the             between ANN. The fields discussed by ANN, such as 
               application  of  systematic  approaches  to  find,  under  a         pattern recognition, pattern association, and simulation 
               given set of conditions, The strongest mix of materials              and  optimization  of  algorithms,  can  also  be  very 
               and/or process variables available that will contribute to           difficult to solve. 
               the manufacture of a Pharmaceutical quality commodity                          
               Any time it is made, with predetermined and specified                         ANN is a digital tool that emulates the human 
               characteristics [1].                                                 brain's  intertwined  neural  processes  and  the  human 
                                                                                    brain's capacity to understand and overcome issues by 
                        An alternative  approach  to  the  mathematical             pattern  recognition  [10].  Through  modelling data and 
               methods of RSM is artificial neural networks (ANN).                  understanding  patterns  in  dynamic  multi-dimensional 
               For low dimensionality or for simple functions being                 interactions  is  occurs  in  between  input  and  output  or 
               approximated,  RSM  fits  well.  This  polynomial  form,             target  sets  of  data,  ANN  simulates  the  learning 
               however, has limitations. Basically, only one predictor              behaviour  of  the  human  brain.  If  an  ANN  has  been 
               variables or a small order polynomial can be suited to               licenced,  responses  for  a  given  range  of  input 
               RSM.  First  an  effective  RSM  for  each  dependent                conditions  may  be  predicted  and  expected  and  can 
               variable can be designed to maximise response surface                therefore  be  used  to  optimise  both  formulation  and 
               problems [2, 3].                                                     process variables in order to produce and deliver high-
                                                                                    quality, secure and effective dosage forms [16]. 
                        For  this  function,  a  computer  optimization                       
               technique based on a reaction surface method (RSM)                   2.   Advantages & Disadvantages OF ANN  
               has been commonly used [4]. However, based on the                    2.1. Advantages 
               second-order  polynomial  theorem,  commonly  used  in                   When  the  response  variables  are  strongly  non-
               RSM, the calculation of pharmaceutical responses often                    linear, ANN reliably forecasts outcomes. 
               limited to low stages. The effect of this restriction may                The dimensionality question curse also supervises a 
               be  the  weak  assessment  of  ideal  formulations.  We                   neural network which obscures attempts to model a 
               developed  a  multi-objective  parallel  optimization                     large number of variables in nonlinear functions. 
               strategy to resolve the limitations in RSM in which an                   Networks are more welcoming than mathematical 
               artificial neural network (ANN) was implemented [5-7].                    simulation  packages  to  fragmented  and  noisy 
               ANN  is  a  computer-based  learning  device  that  can                   knowledge. Therefore, for preparation, literature or 
               mimic the human brain's neurological processing ability                   historical evidence can also be used. 
               [8].                                                                     It does not require any previous knowledge of the 
                                                                                         problem's underlying mathematical nature. 
                        The artificial neural network, first invented in                The  Neural  Network  has  a  special  ability  to 
               the  early  1960s,  only  started  to  expand  progressively              recognise a pattern. 
               during the early-1980s along with launch for modern                      They are efficient when fitted with neural nets but 
               neural  network  modelling  &  developments  with                         can leading to a decline in the timing and expense 
               computer technology. Neural networks have since been                      of product innovation. 
               used  successfully  in  a  number  of  fields,  including                In  comparison  to  mathematical  simulations,  an 
               banking,    energy,    health,    retail,  manufacturing,                 ANN       model       functions      without      data   
               telecommunications  and  defence.  Future  uses  of  the                  transformations on experimental data. 
               Artificial Neural Network (ANN) In medicinal research                    ANN does not require any assumption as to  the 
               methodology range from experimental analysis results,                     significance of the links between the materials of 
               medication and dosage forms designed bio pharmacy to                      the  formulation,  as  well  as  the  properties  of  the 
               clinical pharmacy [9]. The use of artificial intelligence,                formulations [7, 17]. 
               such as artificial neural (ANN) networks, has been used                    
               in  pharmaceutical  sciences  to  generate  and  refine              2.2. Disadvantages 
               dosage  forms  in  an  increasingly  growing  area  of                   The biggest limitation of ANN was how they are 
               knowledge discovery and data mining [10-15]. In recent                    by  default,  computer  systems;  Interaction  which 
               years,  the  implementation  of  ANN  in  the  field  of                  network  gets  cannot  readily  represented  as 
               pharmaceutical  production  has  gained  attention.  The                  statistical format. 
               fundamental theory of simultaneously optimising many                     In  designing  a  model,  the  primary  risk  is 
               ANN-based  pharmaceutical  responses  has  previously                     overworking,  a  condition  in  when  the  neural  net 
               been extensively developed [5-7].                                         begins to replicate stimulus similar to a particular 
                         
               © 2021 |Published by Scholars Middle East Publishers, Dubai, United Arab Emirates                                                                                  369 
                
                
                                                                                                                                                
                                                                                                                                                
                                                                   Manoj Kumar Ananthu et al., Saudi J Med Pharm Sci, Aug, 2021; 7(8): 368-378 
                    section in the training data. The drawbacks could               3.   Artificial Neural Networks in Optimization of 
                    be  eliminated  if  described  above  by  conducting                 Pharmaceutical Formulations 
                    network inspection.                                                 The term Optimize is defined as to make perfect, 
                   ANN includes the use of specialised technologies,                    effective, or functional as possible. 
                    while RSM can carry out using   earliest tools such                 It is the process of finding the best way of using the 
                    as EXCEL (response surface methodology) [18].                        existing resources while taking in to the account of 
                                                                                         all  the  factors  that  influences  decisions  in  any 
                                                                                         experiment as shown in table 1. 
                                                                                
                               Table-1: Artificial Neural Networks in Optimization of Pharmaceutical Formulations 
                Dosage           Applications                                  Author Name           ANN Types             Software used 
                Forms 
                Pre-             The physiochemical characteristics of the     N K Ebube             Multi-Layer Back      CAD : Chem[19]  
                formulation      Amorphous polymers                                                  Propagation 
                Pre-             A new pre - formulation tool for              Josephine LP          Radial Basis          Visual Basic 5.0 
                formulation      microcrystalline cellulosis grouping                                Function Networks     language [20] 
                Pre-                                                                                 Generalized           STATISTICA 
                formulation      The drug stability prediction                 I.Svetlana            Regression Neural     [21] 
                                                                                                     Networks 
                Tablets          The bi-modal delivery of drugs                A.Ghaffari            Multi-Layer           CPC-X [22] 
                                                                                                     Perceptron - FFN 
                Tablets          Extended Release of Diclofenac Sodium         Branka I              Multi-Layer           STATISTIA[23]  
                                                                                                     Perceptron 
                                                                                                     Generalized 
                Tablets          Tablets of Aspirin Extended Release           Svetlana I            Regression Neural     STATISTIA[24]  
                                                                                                     Networks 
                Tablets          CR(Controlled release) tablets formulation    B.Panagiotis          FFBP                  SNNS [25] 
                                 with Nimodipine 
                Tablets           controlled release drug delivery             Takahara              Multi-Layer           Kalman filter 
                                                                                                     Perceptron            algorithm[6] 
                Tablets          Time-dependent tablets that provide rapid     Huijun Xie            Back propagation      Neuro Shell 2 
                                 and continuous delivery                                             networks              Release[26]  
                                 Diclofenac sodium dissolution from                                  Back propagation       SRC Computer 
                Tablets          preparations of continuous release            Zupancic D            networks              company[27] 
                                                                                                      
                Tablets          Metformin HCl 500mg Sustained Release         Uttam M               Multi-Layer           STATISTICA[28]  
                                 Matrix Tablets                                                      Perceptron 
                                 Dissolution of Salbutamol Sulfate from                              Back propagation      Matlab® R 2008a 
                Tablets          Sustained Release Matrix Preparations         Faith C               networks              [29] 
                                                                                                      
                                 Porosity osmotic pump tablets for                                   Back propagation      Visual Basic 5.0 
                Tablets          salvianolic acid                              Wen-Jin X             networks              language [30] 
                                                                                                      
                                 Several formulation factors and process                             Radial Basis          HSOL 
                Tablets          variables comprise a pharmaceutical           Anand P               Function Networks     algorithm[31]  
                                 formulation. 
                                 Crushing Strength and Disintegration                                Multi-Layer           Camo A/S, 
                Tablets          Time of a High-Dose Plant Extract Tablet      K. Rocksloh           Perceptron            Trondheim, 
                                                                                                                           Norway[32]  
                                 Dissolution Profiles of Acetaminophen                               Multi-Layer           NeuroShell® 
                Beads            Beads Prediction                              Yingxu P              Perceptron            Predictor, Release 
                                                                                                                           2.1[33]  
                Microspheres     Preparation of acrylic microspheres with      N. YUÈ KSEL           Multi-Layer           NeuroShell Easy 
                                 controlled release                                                  Perceptron            Predictor,[34]  
                                                                                                     Back propagation      Visual Basic 5.0 
                Powders          Modeling properties of powders                Aykut Canakci         & Radial Basis        language[35]  
                                                                                                     Function Networks 
                Powders          Powder Flow Modeling.                         Kachrimanis           Back propagation      SNNS[36]  
                                                                                                     networks 
                Pellets          Theophylline pellet controlled-release        Kok kp                Multi-Layer           The NEURAL 
                                 matrix                                                              Perceptron            program[37]  
               © 2021 |Published by Scholars Middle East Publishers, Dubai, United Arab Emirates                                                                                  370 
                
                
                                                                                                                                             
                                                                                                                                             
                                                                 Manoj Kumar Ananthu et al., Saudi J Med Pharm Sci, Aug, 2021; 7(8): 368-378 
                Topical         The O-ethylmenthol (MET) effect on the       K.Takayama           Multi-Layer           Kalman filter 
                Patches         absorption of ketoprofen percutaneously.                          Perceptron            algorithm[38]  
                Topical         Melatonin transdermal delivery               KK.Karunya           Multi-Layer           Basic 5.0 
                Patches                                                                           Perceptron            language [39] 
                Liposomes       formulation parameters for the               S.Narayanaswamy   Multi-Layer              Visual Basic 5.0 
                                Optimization of cytarabine liposomes                              Perceptron            language [40] 
                                Formulation of ketoprofen hydrogel                                Multi-Layer           Program 
                Hydrogel        incorporating o-ethyl-3-butylcyclohexanol    PAO-CHU W            Perceptron            MULTI[11]  
                                as a percutaneous improver of absorption. 
                                A preparation of ketprofen hydrogel                               Multi-Layer           The 
                Hydrogel        containing O-Ethylmenthol as a               Junichi T            Perceptron            computerrogram 
                                percutaneous enhancer of absorption.                                                    ANNOP [38] 
                Emulsion        Paclitaxel Emulsion Carried by               Tianyuan Fan         Probabilistic         ANN and 
                                PEGylation.                                                       Neural Networks       ALCORA [41] 
                Emulsion        Optimizing the concentration of fatty        Jayaram K.           Multi-Layer           NeuroShell 2 [42] 
                                alcohol in the formulation                                        Perceptron 
                                Cross-linked calcium-alginate-
                Gelisphere      pectinatecellulose textural profiling and    Viness P             Multi-Layer           Neuro Solutions 
                                mathematical optimization Acetopthalate                           Perceptron            Version4.2[43]  
                                gelisphere matrices. 
                Granules        Sustaining the release of indomethacin       K.Takayama                                 Visual Basic 5.0 
                                granules                                                                                language [44] 
                Pharmaco -      Modeling of special oral hypoglycemic                             Multi-Layer           NeuroShell 
                kinetics        agents in pharmacokinetics and               Sam HH               Perceptron            Predictor™ [45] 
                                pharmacodynamics 
                Pharmaco -      Prediction of pharmacokinetic parameters     Joseph VT            Multi-Layer           STATISTICA[46]  
                kinetics        from the composition of drugs                                     Perceptron 
                Pharmaco -      The neural network predicted peak            Michael EB           Multi-Layer           Program 
                kinetics        concentrations of Gentamicin and troughs.                         Perceptron            NONMEM [47] 
                Pharmaco -      Quantitative structure- pharmacokinetic                           Generalized           MLFN Algorithm 
                kinetics        relationship for drug delivery properties    YAP CW               Regression Neural     [48] 
                                                                                                  Networks 
               
              4.   ARTIFICIAL         NEURAL  NETWORK  'S                         the  method  by  which  neurons  are  coordinated. 
                   Overview (ANN)                                                 Architecture. ANN is mainly made up of three types of 
                        It is possible to make up a neural network of a           layers as Shown in figure-1. 
              huge number of neurons and the "network" is named 
                                                                              
                                                           Fig-1: Artificial Neural Network                      
                                                                              
              © 2021 |Published by Scholars Middle East Publishers, Dubai, United Arab Emirates                                                                                  371 
               
               
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...Saudi journal of medical and pharmaceutical sciences abbreviated key title j med pharm sci issn print online scholars middle east publishers dubai united arab emirates homepage https saudijournals com review article artificial neural networks in optimization formulations manoj kumar ananthu pavan chintamaneni shakir basha shaik reshma thadipatri nawaz mahammed department pharmaceutics raghavendra institute education research riper autonomous ananthapuramu andhra pradesh india analysis quality assurance doi sjmps vi received accepted published corresponding author abstract network is a computer program based on simulation neurons human brain during the past statistical methods like rsm response surface methodology other are used for development modified release controlled sustained due to draw backs another technique ann has an emerging field cr sr this containing optimized different by also structure developed using discussed helps learning according set data given functioning identifi...

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