clays as nanocarriers

1. Prepared by :
Mayur S. Patil
1st Sem. M.Pharm
Pharmaceutics
PH-109
1
PES’s Modern College of Pharmacy, Nigdi, Pune-44.
2017-18
Guided by:
Mr. U.C. Galgatte
Associate Professor
Department of
Pharmaceutics

2. 2
Contents
 Introduction
 Literature review
 Patents
 Aim & objectives
 Drug –clay mechanism
 Preparation of drug clay complex
 Uses of clays
 Case study
 Conclusion

3. Clay :
Clay is a naturally occurring material composed the primarily of fine grain
minerals which show plasticity through variable range of water contain an which
can be harden when dried or fired .
Clay deposit are most composed of clay mineral and variable amount of trap in
mineral. Clay material have been investigated because of their importance in
agricultural ceramic, pharmaceutical and other uses.
Clay are in expensive material which can be modified by ion exchange metal
metal complex impregnation an acid treatment to develop catalyst with desired
functionality.

4. CURRENT NAMES OF
CLAYS
Origin Main clay mineral
constituents
Remarks
Ball clay Sedimentary Kaolinite Highly plastic, white
burning (Grim, 1962)
Bentonite Volcanic rock alteration or
authigenic
Montmorillonite
Bleaching earth Acid-activated bentonite Decomposed
montmorillonite
Common clay Sedimentary or by
weathering
Various, often
illite/smectite mixed-layer
minerals
General for ceramics
excluding porcelain
China clay Hydrotherma Kaolinite Kaolins from Cornwall
plastic, white burning
Fire clay Sedimentary Kaolinite Plastic, high refractoriness
(Grim, 1962)
Current Names of Clays :

5. NANO CLAY:
Nano clay are mineral which have a high aspect ratio and with at leats one dimensional of the
particle in the nano meter range.
The most important factor is the aspect ratio of clay particale.The clay having platy structure an a
thickness of less than one nano meter are of clays of choice.
The length and width of the choice clay on in the micron range.Aspect ratio of the choice clays
are in the 300:1 to 1500:1 range.The surface area of the exfoliated platelets is usually in the range
of 700 meter sq. per gram.
The nano clays that researcher have concentrated on are listed below:
1. Hydrotalcite
2. Montmorillonite
3. Micafluoride
4. Octasilicate

6. CLASSIFICATION OF CLAY MINERALS:
 Kaolinite serpentine
 Pyrophyllite talc
 Mica
 Chlorite
 Smectite
 Vermiculite
 Palygorskite setiolite

7. PROPERTIES OF CLAY :
 High cation exchnage capacity
 High swelling index
 Adjustable hydrophobic and hydrophilic balance
 Amphoteric behavior
 High external and internal specific surface area
 Complex rheological behavior

8. LITERATURE REVIEW :-
Sr no. Name of the Research Article Name of the author
1.
mechanism of clay-drug interactions.
Raghvendra and R
saraswathi
2. Importance of clay minerals for pharmaceutical, medical and
cosmetic purposes.
Action of minerals including clay for delay of drug action, and as
a carrier–releaser of organic compounds.
M. Isabel Carretero , et al
3. Recent advances of clay minerals in modified drug delivery
system , in pharmaceutical dosage forms and therapeutic uses
Clay polymer nanocomposites for drug delivery systems has been
discussed.
C. Viseras et al.
4. Nanoclay and modified nanoclay showed antibacterial activity.
Modified MMT and nano platelet MMT showed enhanced
cytotoxicity as compared to pristine MMT.
Jiang-Jen Lin et al
5. In pharmaceutical formulations, spas and aesthetic medicines. In
oral formulations (gastrointestinal protectors, laxatives,
tidiarrhoeaics) topical applications and on active organic
principles.
M. Isabel Carrete

9. PATENTS :-
SR NO. PATENT NO. COUNTRY TITLE
1. US20140276484A1 US Clay composite and their
application.
2. US20060147538A1 US Nano composite drug delivery
composition.
3. US9321030B2 US Clay containing thin flims as carriers
of absorb molecule.
4. US20110000672A1 US Clay stabilization with nano
particles.
5. US20160360755A1 US Method of using clay suspension to
prevent viral and phytoplasma
diseases in plants.
6. US20160101129A1 US Medicinal clay preperation.

10. AIM AND OBJECTIVES
 Aim: To study clay as a nano-carrier system.
 Objectives:
1. To study the method of preparation of clays.
2. To study the properties of various types of clays.
3. To study the mechanism of clay in drug delivery system.
4. To study the pharmaceutical applications of clays.

11. Current challenges in clay minerals for drug delivery :
 Besides these classic pharmaceutical uses, clay minerals may be effectively used
in the development of new drug delivery systems (DDS). Strictly speaking, all
pharmaceutical dosage forms are DDS, as they are used to administer drugs mean
to reach the site of action and maintain a certain concentration during treatment.
However, the ultimate therapeutic effect of a pharmaceutical treatment will
depend on several factors.
 factors concern pharmaceutical considerations such as optimal dosage forms and
route of administration, frequency and dose of drug in the dosage forms, etc.
Pharmacology studies the effect of a drug on a patient.
 Pharmaceutical technology works in the area between the drug and the dosage
form, selecting and preparing the most adequate pharmaceutical product. Finally,
biopharmacy studies the evolution of a dosage form (and the drug that it contains)
after administration to the patient.
The need for modified drug delivery systems:

12. RECENT ADVANCES OF CLAY MINERALS IN MODIFIED DRUG DELIVERY
SYSTEMS:
Clay/clay mineral (USA pharmacopoeial
name)
Route of administration Dosage form
Talc Oral Solid (conventional and modified release capsules and
tablets, chewable tablets, and granules) Liquid (drops,
mucilage, solutions, elixir, suspensions, and syrup)
Buccal Chewing gums and tablets
Topical Lotions, ointments, and powders
Activated pulgite Oral Powder
Bentonite Oral Solid (capsules and tablets)
Liquid (suspensions)
Magnesium Aluminum Silicate (MAS) Oral Solid (conventional and modified tablets, granules,
capsules, chewable tablets, and powders)
Liquid (drops, suspensions, and syrups)
Rectal Suspensions
Vaginal Ointments
Magnesium trisilicate* Oral Conventional, modified and chewable tablets
Oral Solid (conventional and modified tablets and capsules,

13. MECHANISMS OF CLAY – DRUG INTERACTION :
 Clay minerals are naturally occurring inorganic cationic exchanger and so
they may undergo ion exchange with basic drugs in solution.
 Sometimes is specially montmorinnonite and saponite have been the more
commonly study of their higher cat ion exchange capacity compare to other
pharmaceutical silicates such as talc kaolin and fibrous clay
 There are several mechanism that may be involve interaction between clay
mineral and organic molecules.

14. INTERACTION BETWEEN CLAY MINERAL AND ORGANIC COMPOUNDS
Mechanism Mineral example Organic functional group
involved
Hydrophobic interaction Any clay with neutral sides e.g
Kaolinite
Uncharge non pollar
e.g aromatic
Hydrogen bonding Any clay with oxygen surface
e.g kaolinite
Amines carbonyl
Protonation Any clay with oxygen surface
e.g kaolinite
Amines carbonyl
Ligand exchange Alumino silicate edge sides
ferrious oxide and AL oxide
Carboxylate
Cation exchange Alumino silicate edge sides
ferrious oxide and AL oxide
Heterocyclic N
Cation bridging illite Carboxylate amines

15. Preparation of clay-drug complex :
 Clay particles are dispersed in aqueous drug solution, dispersion are allowed to equilibrate for a
suitable time, and finally solid phases are recovered and dried.
 To entrap bioactive molecules by inducing coagulation in nano clay dispersion
 Dry method specifically helpful for poorly soluble molecule was also reported consisting in
grinding the clay and drug together or putting them in contact at the melting temperature of the
drug.
Extended release system:
 Clays and clays minerals
pharmaceutical grade clay mineral have been extensively applied for prolong release.
 Layer double hydroxide:
LDH can also be used as hold compound because of the positively charge layer presence of inter
layer anions. These compound are specially helpful for retention negative charge biomolecules.

16. CLAY NANOCOMPOSITE PREPARATION:
Depending on the nature of the components used (layered silicate, organic cation
and polymer matrix) and the method of preparation, three main types of
composites may be obtained with association of polymer in clay.
 Exfoliation-adsorption
 Melt intercalation
 Template synthesis
 In situ intercalative polymerization

17. CLAYS AND THEIR FUNCTION IN DELIVERY SYSTEM
Type Function Drug
MgAl, MgAlFe layered double
hydroxides
Modified drug release Fenbufen
Montmorillonite Modified drug release Tramadol hydrochloride
Hydrotalcite-like Modified drug release Paracetamol

18. PHARMACEUTICALAPPLICATIONS OF CLAYS:
Lubricant
Help to easily and effectively disperse active ingredients; facilitate
tablet elaboration
Desiccants
Keep pharmaceutical preparation dry and assist their conservation as
well as prevent disintegration (anhydridte and periclase)
Diluents and binders
Diluents facilitate administration of drug to patient at mg and ml dose
and facilitate the compaction of tablet and granule
(smectites,talc;gypsum)

19.  Pigments
Improve organoleptic properties improve taste smell and color (hematite,calcite)
 Emulsifying, thickening and ant caking agent
Avoid segregation of component and prevent formation of sedimentation they are
used in liquid pharmaceutical preparation (palygorskites kaolinite and talc)

20.  Flavor correctors:
Mask unpleasant flavor or taste of certain active ingredients
(smectites,palygorskites)
 Isotonic agent:
Liquid preparation of drugs must be isotonic neither gain or loose water when
cell in contact with solutions(halite)
 Carrier and release of active ingredient:
Clay minerals serve as carrier releasing active ingredients under specific
conditions (smectites,palygorskites)

21.  Antidiarroels and antacid:
Palygorskite and sepiolite can act as adsorbent for toxin bacteria and even viruses
in intestine
In addition they are protective coating for stomach and intestine
 Adsorbent and protectors:
Magnesium trisilicate also has high adsorption capacity and has also been
proposed as treatment for ciprofloxacin overdose and toxicity

22.  Medicinal clays have been widely used in medicine to Protect the skin against
external physical or chemical substances
 Purify blood
 Reduce or eliminate infections
 Heal ulcers
 Fight against certain allergies
 Alleviate joint pain (anti-inflammatory)
 Act as antimicrobial and antifungal agents

23. Uses of Fibrous Clay Minerals in Pharmaceutical Product
Pharmacopeial Dosage Form Administration Functional Category Examples
Excipients
Magnesium trisilicate Solid Oral Adsorbent, glidant,
binder and disintegrant
Conventional and
modified release tablets
liquid Oral Suspending and
anticaking agent
Oral and topical
suspensions
Active principles
Attapulgite Solid/ liquid Oral Antidiarrhoeal Antidiarrhoeal
suspension
formulations and
immediate release
tablets
Solid/ liquid Oral Antacid Antacid
Magnesium trisilicate Solid/ liquid Oral Antacid Antacid suspensions
and tablets

24. Halloysite clay nanotubes for resveratrol delivery to cancer cells
Resveratrol is a polyphenolic compound possessing antiproliferative properties, and other biological
activities but its usage is limited because of low solubility in water. In view of its importance in
medical applications it is necessary to encapsulated it inside a nano-delivery system.
50-nm diameter halloysite nanotubes can be used as drug delivery system because of their
biocompatibility and allowing drug sustained release. These tubes can be loaded with a wide range of
compounds following their retention and slow controlling the release with further surface
modifications, including the end-stopper formation.
Halloysite clay can be considered as green and natural nanocarriers for hydrophobic drugs
encapsulation. Resveratrol-loaded clay nanotubes showed slow 48-hour release with a constant release
rate with time.
An additional functionalization for controlling the release rate was made using layer- by-layer
polyelectrolyte multilayer coating onto the tube external surface and further decrease of release rate
was demonstrated. Based on these results, halloysite clay nanotubes are proposed as novel natural
pharmaceutical carriers.
Case study: I

25. we have demonstrated a facile strategy for preparing a novel gene delivery system of
HNTs-based multifunctional nanocarrier for loading, intracellular delivering, and cellular
tracking of siRNA. The developed f-HNTs carriers exhibited efficient intracellular
transporting and high delivery efficiency of siRNA.
Furthermore, the f-HNTs-mediated siRNA could effectively induce the knockdown of the
target survivin gene in PANC-1 cells and improve the antitumor activity of siRNA.
Therefore, with the advantages of unique tubular structure, large aspect ratio,
abundant availability, good biocompatibility, and high mechanical strength, these
functionalized HNTs material are expected to be widely exploited as multifunctional delivery
vehicles for cancer therapy and imaging applications.
Multifunctional nanocarrier based on clay nanotubes for efficient
intracellular siRNA delivery and gene silencing
Case study: II

26. Marketed products of clays:

28. Conclusions:
A variety of clay minerals are used as excipents in pharmaceutical preparation
Certain desirable physical and physiochemical properties of clay minerals make
them ideal for pharmaceutical prepration Clay minerals as active ingredients
have medical health applications.
Development for protective and controlled delivery of various functional
compounds is of particular interest clay minerals also have various applications
in agricultural, environmental, cosmetic industries
Nanoclays as drug vehicle for controlled release drug is one of the born age area
in medicinal application nanoclays as great potential as compared to polymer
and nanotubes in DDS. the investigation of clay drug interaction and release
mechanism is esstintial for the clay based drug delivery systems

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