Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

‫ ٔجذأ ثظُ هللا‬... ْٛ١‫ ِظزؾلزاد اٌؼ‬ٟٕ‫ؼ‬٠ Ocular ‫ ػجبرح ػٓ اي‬ٛ٘ٚ ‫ّبْ ٘زجذأ رؼزػ عشء٘ب‬٠‫رح ا‬ٛ‫ دوز‬... ‫ب ػجبة‬٠ ُ‫ى‬٠‫اس‬

Definition: They are sterile pharmaceutical preparations that applied topically to the eye to
treat surface or intraocular conditions.

 The most commonly employed ophthalmic dosage forms are solutions, suspensions,
and ointments.
 But these preparations when instilled into the cul-de-sac are rapidly drained away from
the ocular cavity due to tear flow and lacrimal nasal drainage.
 The newest dosage forms for ophthalmic drug delivery are: gels, gel-forming
solutions, ocular inserts, intravitreal injections and implants.

‫ب‬ٍٙ‫ِّىٓ ادخ‬ٚ‫خ أ‬١‫ٓ ٌّؼبٌغخ اٌؾبالد اٌظطؾ‬١‫ اٌؼ‬ٍٝ‫ب ً ػ‬١‫كؼ‬ِٛ ‫كغ‬ٛ‫ْ ِؼمّخ ر‬ٛ‫خ اُ٘ ؽبعخ السَ رى‬١ٔ‫ذال‬١‫ ِظزؾلزاد ؿ‬ٟ٘
.ٍٟ‫ٓ ػؼبْ رؼبٌظ ِزف داخ‬١‫ٖ اٌؼ‬ٛ‫ع‬

.ُ٘‫اٌّزا‬ٚ ‫اٌّؼٍمبد‬ٚ ً١ٌ‫ اٌّؾب‬ٟ٘ ‫ػب‬

ً ٛ١‫ْ ػ‬ٛ١‫أوضز أػىبي عزػبد اٌؼ‬
‫ذ‬١‫ ثؼ‬ٞ‫ رـزف اٌؾبعخ د‬ٚ‫ب رزمفً ا‬ٙٔ‫ي ا‬ٚ‫ثزؾب‬ٚ ‫ كذ٘ب‬ٟ‫ ؽبعخ ثزبخذ ػىً دفبػ‬ٞ‫ب ا‬ِٕٙ ‫ٓ ٌّب رمزة‬١‫ ِؼىٍخ ٕ٘ب اْ اٌؼ‬ٍٟٕ‫٘زمبث‬
‫عخ‬ٚ‫د اٌٍش‬ٚ‫ ثش‬ٟٔ‫ك ا‬٠‫ ػٓ مز‬ٞ‫ي ٔؾً اٌّؼىٍخ د‬ٚ‫ٕ٘ؾب‬ٚ ‫ب‬ٕٙ‫ػ‬

ً‫اٌؾمٓ داخ‬ٚ ، ٓ١‫إدراط اٌؼ‬ٚ ، َ‫ال‬ٌٙ‫ً ا‬١‫ً رؼى‬١ٌ‫ِؾب‬ٚ ، ‫خ‬١ِ‫ال‬ٌٙ‫اد ا‬ٌّٛ‫ ا‬:ٟ٘ ‫خ‬١ٕ١‫خ اٌؼ‬٠ٚ‫ً األد‬١‫ؿ‬ٛ‫أؽذس أػىبي اٌغزػبد ٌز‬
.‫اٌغزطبد‬ٚ ٟ‫اٌغظُ اٌشعبع‬

The Eye:
a unique organ, both anatomically and physiologically containing several widely varied
structures with independent physiological functions.

 The complexity of the eye provides unique challenges to drug delivery strategies.

‫اطغ ِغ‬ٚ ‫ ٔطبق‬ٍٝ‫ػخ ػ‬ٕٛ‫بوً اٌّز‬١ٌٙ‫ذ ِٓ ا‬٠‫ اٌؼذ‬ٍٝ‫ ػ‬ٞٛ‫ؾز‬٠ ، ‫خ‬١‫ع‬ٌٛٛ١‫اٌفظ‬ٚ ‫خ‬١‫ؾ‬٠‫خ اٌزؼز‬١‫ ِٓ إٌبؽ‬، ٗ‫ػ‬ٛٔ ِٓ ‫ذ‬٠‫ فز‬ٛ‫ػل‬
.‫خ ِظزمٍخ‬١‫ع‬ٌٛٛ١‫ظبئف فظ‬ٚ

.‫اء‬ٚ‫ً اٌذ‬١‫ؿ‬ٛ‫بد ر‬١‫غ‬١‫ذح الطززار‬٠‫بد فز‬٠‫ٓ رؾذ‬١‫ذ اٌؼ‬١‫فز رؼم‬ٛ٠ 

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Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

Anatomy and Physiology of the Eye:

The eye consists of three layers:

1. Outer fibrous layer (Sclera 2/3, cornea1/3)

2. Middle vascular layer (iris, choroid)
3. Inner nervous layer (retina)

BARRIERS TO DRUG PERMEATION:

 Compared with drug delivery to other parts of the body, ocular drug delivery must
overcome important challenges posed by various ocular barriers to deliver the appropriate
dose at the appropriate place.

Lachrymation, effective drainage by the nasolacrimal system, the inner and outer blood-retinal
barrier, the impermeability of the cornea, and inability of other non-corneal structures to absorb
compounds make the eye exceedingly impervious to foreign substances.

 While these innate barriers are advantageous for hindering the invasion of undesired
molecules, pathogens, and particulates, they pose significant challenges to the delivery of
ocular drugs.

complex defence ‫ب اي‬ّٙ‫د ؽبعخ اط‬ٛ‫ع‬ٚ ‫غخ‬١‫ػىٍٗ ٔز‬ٚ ٗ‫ج‬١‫ش ثززو‬١ِّ ُ‫ٓ دٖ أوزز عشء ِٓ اٌغظ‬١‫ اٌؼ‬ٜ‫ي ؽبعخ ػٕذ‬ٚ‫ا‬
‫ع‬ِٛ‫ اٌذ‬ٜ‫ب س‬ٍٙ‫ذخ‬٠ ‫ت‬٠‫ عظُ غز‬ٜ‫ٓ ِٓ ا‬١‫ اٌؼ‬ٝ‫ثزؾ‬ٚ ‫ب ثزذافغ‬ٙٔ‫خ أ‬١ّ٘‫ب أ‬ٙ١ٌ ‫بد دفبع‬١ٌ‫ آ‬ٜ‫ د‬barriers ‫ اي‬ٚ‫أ‬mechanism
ْ‫وّب‬ٚ .. َ‫ اٌذ‬ٌٝ‫ب إ‬ِٕٙٚ ٓ١‫ذخً ِٓ خالؽ اٌؼ‬٠ ‫ وبئٓ ِّزف‬ٚ‫ عظُ أ‬ٜ‫ّٕغ ا‬١‫ ث‬blood retinal barrier ّٗ‫ؽبعش اط‬ٚ
‫ب‬ٕٙ‫ت ػ‬٠‫ عظُ غز‬ٜ‫ِخ أل‬ٚ‫ذح اٌّمب‬٠‫ٓ ػذ‬١‫ اٌؼ‬ٍٝ‫خ‬١‫ت دٖ ث‬٠‫ ِزوت غز‬ٜ‫ٓ ِغ رّزؾ ا‬١‫ ِٓ اٌؼ‬ٜ‫األعشاء األخز‬ٚ ‫خ‬١ٔ‫ اٌمز‬ٜ‫ػٕذ‬

ٗ‫اع‬ٛ‫ ر‬other drug delivery ‫ٓ ثبٌّمبرٔخ ثبي‬١‫خ اٌخبؿخ ثبٌؼ‬٠ٚ‫ األد‬ٍٝ‫ ثزخ‬ٜ‫اعش د‬ٛ‫ إال أْ اٌؾ‬ٜ‫ثض ثبٌزغُ ِٓ اٌفبئذح د‬
‫ ثزبػخ‬bioavailability ‫ اي‬ٍٝ‫ب ثزأصز ػ‬ٙٔ‫ أ‬ٜ‫ ا‬site of action ‫اي‬ٚ ‫ثخ‬ٍٛ‫خ اٌّط‬١ّ‫اء ثبٌى‬ٚ‫ؿً اٌذ‬ٛ‫ رمذر ر‬ٜ‫ب اسا‬ٙٔ‫ ثإ‬ٜ‫رؾذ‬
.‫ا‬ٚ‫اٌذ‬

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Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

Factors affecting drug availability:

1. Rapid solution drainage by gravity, induced

Lachrymation, blinking reflex and normal tear turnover  poor retention time

2. The retention of the drug at the site of action is poor

 Due to the low tear volume (7 µl for the blinking eye, 30 µl for the non-blinking eye).
 The typical volume of a drop of a solution formulation is 50 µl and the majority of the
dose is lost either through spillage on to the face or via the lacrimal duct.

‫ب‬ٙ‫ٓ ٔفظ‬١‫ اٌؼ‬ٟ‫ب ف‬ٙ١‫ ٘الل‬ٌٍٟ‫اعش ا‬ٛ‫ٗ ثؼق اٌؾ‬١‫ ارفمٕب اْ ف‬... ٓ١‫ا داخً اٌؼ‬ٚ‫د اٌذ‬ٛ‫ع‬ٚ ٍٝ‫ ػ‬ٞ‫ ٘زأصز‬ٌٍٟ‫اًِ ا‬ٛ‫ ثؼق اٌؼ‬ٞ‫د‬

ً‫اعذ٘ب داخ‬ٛ‫ فززح ر‬ٌٟ‫ثبٌزب‬ٚ ‫ ؽبعخ‬ٞ‫ب ا‬ِٕٙ ‫ لزثذ‬ٌٛ ً‫ي رمف‬ٚ‫ٓ ثزؾب‬١‫ اٌؼ‬ٛ٘ ٌٍٟ‫ ا‬Blinking reflex ‫ب‬ّٙ‫ٗ ؽبعخ اط‬١‫ٌٕب اْ ف‬ٛ‫ل‬
‫ٍخ عذاا‬١ٍ‫ ل‬ٝ‫ٓ ٘زجم‬١‫اٌؼ‬

ٝ‫ٓ ثم‬١‫ب اٌّزُ٘ ٌىٓ فبٌؼ‬ٙ١‫زح رمذر رظزخذَ ف‬١‫ ِظبؽخ وج‬ٟ‫ ٘زالل‬ٞ‫ اٌغٍذ ػبد‬ٍٝ‫ ٘زؾن ِضال ِزُ٘ ػ‬ٌٛ ‫ٌه أذ‬ٛ‫م‬١‫ ؽبعخ ث‬ٟٔ‫رب‬
‫ ِجززمفٍغ ٌىٓ مجؼب‬ٟٕ‫ؼ‬٠ Blinking ‫ّخ ِجزؼٍّغ‬١ٍ‫ٓ ط‬١‫ اٌؼ‬ٌٛ ‫ ؽبٌخ‬ٟ‫دٖ ف‬ٚ ٚ‫ىز‬١ِ 03 ٌٟ‫ا‬ٛ‫ٍخ عذا ؽ‬١ٍ‫ب ل‬ٙ‫ب اْ ِظبؽز‬ٙ‫ِؼىٍز‬
‫أذ اؿال اٌمطبرح ِضال‬ٚ ... ٚ‫ىز‬١ِ 7 ‫اء ي‬ٚ‫ب اٌذ‬ٙ١‫ ٘زمغز رظزخذَ ف‬ٌٍٟ‫ؿً اٌّظبؽخ ا‬ٛ‫ي رمفً ثز‬ٚ‫ب ثزؾب‬ٙٔ‫خ ا‬١‫ؼ‬١‫اٌؾبٌخ اٌطج‬
ٓ١‫ثزٕشي ثزا اٌؼ‬ٚ ‫ اٌغزػخ‬ٟ‫ؾـً فمذ ف‬١‫ ث‬ٟٕ‫ؼ‬٠ 03 ‫ز‬١‫ٓ ِجزظزؾٍّغ غ‬١‫اٌؼ‬ٚ ٚ‫ىز‬١ِ 03 ٌٟ‫ا‬ٛ‫اؽذح ؽ‬ٌٛ‫ب فبٌّزح ا‬ِٕٙ ‫ٕشي‬١‫ث‬

‫ب‬ٙ‫ف‬ٛ‫ال ٔؼ‬٠ ... ٗ‫اء ٔفظ‬ٚ‫ٓ ثظجت اٌذ‬١‫ اٌؼ‬ٟ‫اء ف‬ٚ‫د اٌذ‬ٛ‫ع‬ٚ ًٍ‫ٗ ِؼبوً ِّىٓ رم‬١‫وّبْ ف‬

3. Physicochemical characteristics of the drug substance

 The cornea is a membrane barrier containing both lipophilic and hydrophilic layers
 So, it is permeated effectively by drugs having lipophilic and hydrophilic characteristics.
Lipophilic agents of low molecular weight follow.

Transcorneal transport by passive diffusion and obey Fick’s first law of diffusion:

J = - D. d Cm / dx

‫ٗ ؟؟‬١ٌ ‫ مت‬Lipophilic ‫عشء‬ٚ Hydrophilic ‫ْ عشء‬ٛ‫اء رى‬ٚ‫ؼخ اٌذ‬١‫ السَ مج‬ٟ‫ؼ‬١‫ اٌطج‬ٟ‫لبٌه ف‬

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Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

‫ٌخ مت‬ٛٙ‫ ثظ‬ٞ‫ؼذ‬٠ ْ‫ز ػؼب‬١‫ْ ؿغ‬ٛ‫ى‬٠ ّٗ‫وّبْ ؽغ‬ٚ ‫ اوزز‬Lipophilic ‫ؼزخ‬١‫ْ مج‬ٛ‫ى‬٠ َ‫ غؼبء الس‬ٞ‫ذخً ِٓ ا‬٠ ‫اء‬ٚ‫ػؼبْ اٌذ‬
Hydrophilic ‫خ‬١‫ خبؿ‬ٚ‫ْ ػٕذٖ ثزد‬ٛ‫ى‬٠ َ‫ الس‬ٌٟ‫ثبٌزب‬ٚ Aqueous ْٛ‫ى‬١‫دٖ ث‬ٚ ٓ١‫ طبئً اٌؼ‬ٟ‫الل‬١٘ ٓ١‫ي مجمخ ٌٍؼ‬ٚ‫ ا‬ٞ‫ؼذ‬٠ ‫ٌّب‬
ٓ١‫ طبئً اٌؼ‬ٟ‫ ف‬ٞ‫ؼذ‬٠ٚ ‫ة‬ٚ‫ذ‬٠ ‫مذر‬٠ ْ‫ػؼب‬

4. Protein bound drugs

 Are incapable of penetrating the corneal epithelium because of the size of the protein-
drug complex
 Tears contain 0.6 – 2% of protein (albumin, globulin). Disease states raise the protein
level

ٞ‫ٕبد د‬١‫ر‬ٚ‫زفبػً ِغ اٌجز‬٠ ‫اء لذر‬ٚ‫ اٌذ‬ٍٛ‫ٍخ ف‬١ٍ‫ٕبد ثٕظجخ ل‬١‫ر‬ٚ‫ب ثز‬ٍٙ‫د ثذاخ‬ٛ‫ع‬ِٛ ْٛ‫ى‬١‫ٓ ث‬١‫اء اْ اٌؼ‬ٚ‫د اٌذ‬ٛ‫ع‬ٚ ‫ق‬ٛ‫ؼ‬١٘ ًِ‫اخز ػب‬
.ٓ١‫ ِٓ خالي مجمخ اٌؼ‬ٞ‫ؼذ‬٠ ‫ؼزف‬١٘ ‫ ِغ‬ٌٟ‫ثبٌزب‬ٚ ‫ز‬١‫ْ ؽغّٗ ِج‬ٛ‫ى‬١‫دٖ ث‬ٚ ‫ِجٍىض‬ٛ‫ْ و‬ٛ‫ى‬١٘

Required characteristics to optimize ocular drug delivery system:

 Sterile

 Non irritative and comfortable form

 Simplicity of instillation for the patient.

 Good corneal penetration.

 Prolong contact time with corneal tissue.

 Appropriate rheological properties

‫ٕخ‬١‫ ِؼ‬pH ٌٗ ْٛ‫ى‬١‫اء ث‬ٚ‫ د‬ٞ‫ مجؼب ا‬.... ٓ١‫ظ ٌٍؼ‬١ٙ‫ظجت ر‬٠ ٚ‫خ ا‬١‫ؼٍّغ ؽظبط‬١ِ ٓ١‫ اٌؼ‬ٟ‫ ارؾن ف‬ٌٛٚ ُ‫ْ اٌّظزؾلز ِؼم‬ٛ‫ى‬٠ َ‫الس‬
pH ‫اي‬ٚ ‫ٗ اٌّظزؾلز‬١‫ ٘زظزخذَ ف‬ٌٍٟ‫ ٌٍّىبْ ا‬pH ‫ ٔفض اي‬ٚ‫ ثزبػزٗ ِٕبطجٗ ا‬pH ‫ْ اي‬ٛ‫ى‬٠ ‫ف‬ٚ‫السَ ػؼبْ اطزخذِٗ اٌّفز‬ٚ
‫اؽّزار‬ٚ ٓ١‫ظ ٌٍؼ‬١ٙ‫ؼًّ ر‬١٘ ٖ‫ز وذ‬١‫اء غ‬ٚ‫ ثزبػٗ اٌذ‬pH ‫ اي‬ٍٛ‫ ف‬7.2 – 7.4 ٓ١‫ثزبػخ اٌؼ‬

‫بخذ٘ب‬٠ ٝ‫زك‬١٘ ‫ز ِضال اٌؾمٓ ِغ‬١‫ظزخذِٗ غ‬٠ ٝ‫زك‬٠ ْ‫خ ػؼب‬١‫بؽ‬١‫ثبرر‬ٚ ‫ض‬٠ٛ‫ظزخذَ اٌّظزؾلز ثؼىً و‬٠ ‫مذر‬٠ ‫ق‬٠‫السَ اٌّز‬
‫ٌخ‬ٛٙ‫ظزؼٍّٗ ثظ‬٠ٚ ٌٗ ً‫ٌٗ وً ِب وبْ افل‬ٛٙ‫بخذٖ ثظ‬٠ ‫ق‬٠‫مذر اٌّز‬٠ ‫ ِظزؾلز‬ٞ‫ وً ِب وبْ ا‬ٟٕ‫ؼ‬٠

ٓ١‫شٖ اػبٌظ ؽبعخ داخً اٌؼ‬٠‫ أب ػب‬ٌٛ ٖ‫مجؼب د‬ٚ Cornea ‫ ِٓ غؼبء اي‬ٞ‫ؼذ‬٠ ‫اء‬ٚ‫السَ اٌذ‬

‫ٌخ‬ٛٙ‫ز ثظ‬١‫ اٌزأص‬ٞ‫ذ‬٠ ‫مذر‬٠ ْ‫ٓ فززح ِٕبطجخ ػؼب‬١‫ اٌؼ‬ٟ‫د ف‬ٛ‫ع‬ِٛ ً‫فل‬٠ َ‫الس‬

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Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

ٓ١‫خزط ِٓ اٌؼ‬٠ ‫اء‬ٚ‫ فبٌذ‬ٞٚ‫ٍخ ا‬١ٍ‫عزٗ ل‬ٚ‫ىٕغ اٌّظزؾلز ٌش‬١ِ ‫ش‬١‫ْ ِٕبطجخ ثؾ‬ٛ‫عخ رى‬ٚ‫ اٌٍش‬ٞ‫ْ اٌخـبئؾ ثزبػخ س‬ٛ‫ى‬٠ َ‫الس‬
ٗ‫م‬٠‫لب‬٠ٚ ‫اء‬ٚ‫اعذ اٌذ‬ٛ‫ؾض ثز‬٠ ‫ق‬٠‫ فبٌّز‬ٞٚ‫خ ا‬١ٌ‫عخ ػب‬ٚ‫ْ اٌٍش‬ٛ‫ال رى‬ٚ ‫ثظزػخ‬

‫ٓ؟؟‬١‫ب ٌّظزؾلزاد اٌؼ‬ِٙ‫ ِّىٓ اطزخذ‬ٌٍٟ‫ اٌطزق ا‬ٟ٘ ٗ٠‫مت ا‬

Routes of Ocular drug administration:

1. Topical administration:

 Employed mostly in the form of eye drops, ointments, gels, or emulsions, to treat
anterior segment diseases.
 The most preferred method due to the ease of administration and low cost.
 Upon administration, precorneal factors (solution drainage, blinking, tear film, tear turn
over, and induced lacrimation) and anatomical barriers negatively affect the
bioavailability of topical formulations.
 Viscosity is a factor that can regulate nonproductive absorption, as well as ocular
absorption. Increasing viscosity may decrease drainage rate, prolong precorneal residence
time, and increase ocular absorption.

ً‫فل‬٠ ‫اء‬ٚ‫ش اٌذ‬٠‫ ػب‬ٟٔ‫ٕ٘ب اٌّؼىٍخ ا‬ٚ Cornea ‫ مجمخ اي‬ٍٝ‫ ػ‬ٟٕ‫ؼ‬٠ ... ٓ١‫خ فبٌؼ‬١‫ػ‬ٛ‫ك‬ِٛ ‫ش اػبٌظ ؽبعخ‬٠‫ ػب‬ٌٛ ‫ي ؽبعخ‬ٚ‫ا‬
ٓ١‫ت ِٓ اٌؼ‬٠‫د٘ب اوزز ػؼبْ اٌزظز‬ٚ‫اس‬ٚ ٖ‫ع د‬ٌٕٛ‫ ا‬ٟ‫عخ ف‬ٚ‫ اٌٍش‬ٟ‫ ػؼبْ وذٖ أب ثزؾىُ ف‬... ‫مؼغ‬١‫ِج‬ٚ ٞ‫ اٌطجمخ د‬ٍٝ‫د ػ‬ٛ‫ع‬ِٛ
ٗ‫ز ثزبػ‬١‫ اٌزأص‬ٞ‫ذ‬٠ٚ ‫د فززح‬ٛ‫ع‬ِٛ ً‫فل‬٠ٚ ً‫م‬٠

2. Systemic (Parenteral) Administration

 The blood-aqueous barrier and blood-retinal barrier are the major barriers for the
anterior segment and posterior segment ocular drug delivery, respectively.

 It is ideal to deliver the drug to the retina via systemic administration,

 It is still a challenge because of the blood-retina barrier, which strictly regulates drug
permeation from blood to the retina.

ْ‫ وّب‬ٞ‫ؼذ‬٠ٚ Cornea ‫ مجمخ اي‬ٞ‫ؼذ‬٠ ‫اء‬ٚ‫ٕ٘ب ٘ؾزبط اْ اٌذ‬ٚ ‫ ِضال‬Retina ‫ؼبٌظ اي‬٠ ‫ب‬ٙ‫ٓ ٔفظ‬١‫ب رخغ داخً اٌؼ‬ٙٔ‫مخ ا‬٠‫ مز‬ٟٔ‫رب‬
َ‫ اٌذ‬ٟ‫ ف‬ٞ‫ؼذ‬٠ ‫مذر‬٠ ْ‫ ػؼب‬Hydrophilic ‫ؼخ‬١‫ْ ػٕذٖ مج‬ٛ‫ى‬٠ٚ Blood retina ‫اي‬

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Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

3. Oral Administration

 Oral delivery alone or in combination with topical delivery

 Topical delivery alone failed to produce therapeutic concentrations in the posterior

segment.

 Oral delivery was studied as a possible noninvasive and patient-preferred route to treat
chronic retinal diseases as compared to the parenteral route, restricted accessibility to
many of the targeted ocular tissues limits the utility of oral administration

 Necessitates high dosage to achieve significant therapeutic efficacy. Such doses can
result in systemic side effects. Hence, parameters such as safety and toxicity need to be
considered when trying to obtain a therapeutic response in the eye upon oral
administration.

‫ب‬ٙ‫ٓ ٔفظ‬١‫ ٌٍؼ‬Topical ٖ‫ اخذ ِؼب‬ٚ‫ؽذٖ ا‬ٌٛ ِٗ‫دٖ ِّىٓ اطزخذ‬ٚ ٓ١‫ اٌؼ‬ٟ‫ز ف‬١‫ رأص‬ٞ‫ذ‬٠ ْ‫ ػؼب‬Oral ‫اء‬ٚ‫ اخذ اٌذ‬ٟٔ‫مخ ا‬٠‫ربٌذ مز‬
ٓ١‫ؿً ٌٍؼ‬ٛ١٘ ‫اء‬ٚ‫وّبْ ِغ وً اٌذ‬ٚ ‫ اٌىجذ‬ٟ‫زىظز عشء ِٕٗ ف‬١‫ ث‬Oral ‫زبخذ‬١‫اء ٌّب ث‬ٚ‫ اٌّؼىٍخ اْ اٌذ‬ٝ‫ ثض ٕ٘ب ثم‬.... ٚ‫ثزد‬
‫بدح‬٠‫ اٌغزػبد اٌش‬ٚ‫ ؽـً دٖ ثض ثزد‬ٌٍٟ‫ز ا‬١‫ اٌزىظ‬ٚ‫ف اٌفمذ ا‬ٛ‫مخ أب ِؾزبط عزػخ أوجز ػؼبْ اػزف اػ‬٠‫ اٌطز‬ٟ‫ ف‬ٌٟ‫ثبٌزب‬ٚ
‫زح‬١‫خ وز‬١‫اػزاف عبٔج‬ٚ ً‫ ِّىٓ رؼًّ ِؼبو‬ٞ‫د‬

4. Periocular and Intravitreal Administration

 Not very appealing to patients, these routes are employed partly to overcome the
inefficiency of topical and systemic delivery to the posterior segment.
 Subconjunctival injection bypasses the conjunctival epithelial barrier, which is a rate-
limiting barrier for the permeation of water-soluble drugs.
 The intravitreal injection offers distinct advantages as the molecules are directly inserted
into the vitreous.
 Injection of the solution containing the drug directly into the vitreous via pars plana
using a 30-gauge needle.
 Unlike other routes, intravitreal injection delivers higher drug concentrations to the
vitreous and retina.

Lecture 4 & 5 Page | 6

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

‫ع‬ٌٕٛ‫ ا‬ٟ‫ذ ف‬١‫ؾخ ٌىٓ أب ثظزف‬٠‫ ِز‬ٝ‫مجؼب ِغ ٘زجم‬ٚ ٓ‫رح ؽم‬ٛ‫ ؿ‬ٟ‫اء ف‬ٚ‫بخذ اٌذ‬٠ ‫ق‬٠‫ اْ اٌّز‬... ‫مجؼب ِغ ِفلٍخ‬ٚ ‫مخ‬٠‫اخز مز‬
ٍٝ‫ ػ‬ٕٝ‫ش اطز‬٠‫ أب ِغ ػب‬ٌٛ ‫ ؽبٌخ‬ٟ‫دٖ ف‬ٚ ‫غ‬٠‫ز طز‬١‫ رأص‬ٞ‫ذ‬١٘ ٌٟ‫ثبٌزب‬ٚ ‫ز‬١‫لذ ؿغ‬ٚ ٟ‫ٓ ف‬١‫زح ٌٍؼ‬١‫بد وج‬١ّ‫اء ثى‬ٚ‫ؿً اٌذ‬ٛ١‫دٖ ث‬
‫ خذٔب٘ب لجً وذح‬ٌٍٟ‫ّزؾ ثبٌطزق ا‬٠ ‫اء‬ٚ‫ز ٌؾذ ِب اٌذ‬ٙ‫اٌّؼىٍخ ػ‬

CLASSIFICATION OF OCULAR DRUG DELIVERY SYSTEMS:

A. Topical Eye drops:

1- Solutions:

Definition: they are sterile solutions, essentially free from foreign particles, suitably
compounded and packaged for instillation into the eye.

Problem: liquid formulation with semi solid consistency only when it is placed in the
conjunctival or corneal  easy installation of the solution

Viscosity enhancers: Synthetic polymers, such as polyvinyl alcohol (PVA),

polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), polyacrylicacid (PAA)

 Nearly all the major ophthalmic therapeutic agents are water-soluble salts.

‫ اول حاجة التقليدية زي المحاليل او القطرات‬... ‫بنقسم المستحضرات لتقليدية وغير تقليدية‬

ْ‫ً ا‬ٙ‫مجؼب ِٓ اٌظ‬ٚ ‫ْ ؽظبطخ عذا‬ٛ‫ٓ ثزى‬١‫جخ الْ اٌؼ‬٠‫ئبد غز‬٠‫ عش‬ٞ‫خ ِٓ ا‬١ٌ‫خب‬ٚ ‫ ِظزؾلزاد ِؼمّخ مجؼب‬ٞ‫اٌمطزاد د‬
ٓ١‫ اٌؼ‬ٟ‫اطزخذَ اٌمطزاد ف‬

ً‫ ػؼبْ اؽ‬... ً‫م‬١٘ ٓ١‫ اٌؼ‬ٟ‫ٗ ف‬١‫اعذ ف‬ٛ‫ ٘زز‬ٌٍٟ‫لذ ا‬ٌٛ‫ ا‬ٚ‫ ا‬Contact time ‫ اي‬ٌٟ‫ثبٌزب‬ٚ ‫عخ خبٌؾ ٕ٘ب‬ٚ‫غ ٌش‬١‫ اْ ِف‬:‫ب‬ٙ‫ج‬١‫ػ‬
‫عخ‬ٚ‫د اٌٍش‬ٚ‫اد رش‬ِٛ َ‫ السَ اطزخذ‬ٞ‫اٌّؼىٍخ د‬

‫فمذ‬١‫ٗ عشء ِٓ اٌغزػخ ث‬١‫ ف‬ٌٟ‫ثبٌزب‬ٚ ٓ١‫زح اوجز ِٓ ِظبؽخ اٌؼ‬١‫ْ وج‬ٛ‫ ِبرفمٕب اْ ٕ٘ب ؽغُ إٌمطخ ِٓ اٌمطبرح ثزى‬ٞ‫ ِؼىٍخ س‬ٟٔ‫رب‬

Lecture 4 & 5 Page | 7

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

ْ‫ ٘ؾزبط ا‬ٌٟ‫ثبٌزب‬ٚ ‫ب‬٠‫ز‬١‫ اٌجىز‬ّٛٔ ‫ؾفش‬١‫خ دٖ ث‬٠‫د اٌّب‬ٛ‫ع‬ٚ ْ‫ وّب‬.... ً‫خ ثزبػزٗ ثزم‬١‫ اٌضجبر‬Solution ‫ ؽبٌخ اي‬ٟ‫دح ف‬ٛ‫ع‬ٚ ‫اء‬ٚ‫اٌذ‬
‫ب‬ِٙ‫ٕفؼغ رظزخذ‬١ِٚ ‫ز‬ٙ‫ٌه لذاَ ػ‬ٛ‫م‬١‫ ارفزؾذ ث‬ٌٍٟ‫اد ؽبفظخ ػؼبْ وذح ِؼظُ اٌمطزاد ا‬ِٛ ‫ف‬١‫اك‬

2- Suspensions:

 If the drug is not sufficiently soluble, it can be formulated as a suspension.

 Suspension is desired to improve stability, bioavailability, or efficacy.
 Suspensions are required to be made with the insoluble drug in a micronized form to
prevent irritation or scratching of the cornea, usually 95% or more of the particles have a
diameter of 10 µm or less.

َ‫ الس‬ٝ‫ ٕ٘ب ثم‬.... Suspension ‫رح‬ٛ‫ ؿ‬ٟ‫ ٘ؾلزٖ ف‬ٌٟ‫ثبٌزب‬ٚ ً١ٌ‫ٗ ِغ ٘مذر اطزخذَ اٌّؾب‬٠‫ اٌّب‬ٟ‫ثغ ف‬ٚ‫ذ‬١‫اء ِج‬ٚ‫ب د‬٠‫ ِؼب‬ٌٛ
‫ت‬١‫ ِؼذي اٌززط‬ٚ‫ ا‬Sedimentation rate ‫ ؽبعخ اي‬ٟٔ‫رب‬ٚ ‫ب‬ِٙ‫ ٘ظزخذ‬ٌٍٟ‫ئبد ا‬٠‫ال ؽغُ اٌغش‬ٚ‫ ا‬... ٓ١‫ ِٓ ؽبعز‬ٌٟ‫اخذ ثب‬

‫ز‬١‫ السَ اطزخذَ ؽغُ ؿغ‬ٌٟ‫ثبٌزب‬ٚ ٓ١‫ اٌؼ‬ٟ‫ؼ ف‬٠‫زح ػؼبْ ٘زؼًّ رغز‬١‫ئبد وج‬٠‫ٕفؼغ اطزخذَ عش‬١ِ ‫ئبد لبٌه‬٠‫ ؽبٌخ ؽغُ اٌغش‬ٟ‫ف‬
ٚ‫ىز‬١ِ 03 ٓ‫ذع ػ‬٠‫ش‬٠‫ِب‬

َ‫ ِؼٍك السَ ٔزعٗ لجً االطزخذا‬ٞ‫مجؼب ا‬ٚ ‫م‬ٛ‫غ مجؼب ػؼبْ الذر اطزخذَ اٌغزػخ ِظج‬٠‫ْ طز‬ٛ‫ى‬٠ ‫ئبد‬٠‫ت اٌغش‬١‫ٕفؼغ رزط‬١ِ

ٓ١‫ ِغ اٌؼ‬Contact time ‫د اي‬ٚ‫ ٘زش‬ٌٟ‫ثبٌزب‬ٚ ً١ٌ‫ افلً ِٓ اٌّؾب‬ٝ‫عخ ٘زجم‬ٚ‫ٕ٘ب اٌٍش‬ٚ

3- Gel-Forming Solutions

Solutions that are liquid in the container and instilled as eye drops but gel on contact with the
tear fluid and provide increased contact time with the possibility of improved drug absorption
and increased duration of therapeutic effect

ٍٝ‫زؾن ػ‬٠ ‫ِغزد ِب‬ٚ ‫ي‬ٍٛ‫رح ِؾ‬ٛ‫ ؿ‬ٟ‫ْ ف‬ٛ‫ى‬١‫ مبٌغ ِٓ اٌؼزوخ ث‬ٛ٘ٚ ٟٕ‫ؼ‬٠ .... ُ٘‫ اخذٔب‬ٌٍٟ‫ٓ ا‬١ٕ‫ ػٕذٖ االر‬ٝ‫جم‬١‫ع دٖ ث‬ٌٕٛ‫ا‬
ٌٍٟ‫ً؟ االرثؼخ ا‬١‫ي ٌغ‬ٍٛ‫زٖ ِٓ ِؾ‬١‫ ٘زغ‬ٌٍٟ‫اًِ ا‬ٛ‫ اٌؼ‬ٌٍٟ‫ٗ ا‬٠‫ت ا‬١‫ م‬.... ً١‫ي ٌغ‬ٛ‫زؾ‬٠ٚ ُ‫ز ِغ دعخ ؽزارح اٌغظ‬١‫زغ‬١‫ٓ ث‬١‫ططؼ اٌؼ‬
‫ي‬ٚ‫رؾذ د‬

4- Lysozyme protein in the tear

1- Temperature 2- Ion (Ca) 3- pH
fluid

Lecture 4 & 5 Page | 8

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

B. Semisolid Dosage Forms:

Ointments

 Ophthalmic ointments must be sterile

The chief disadvantages of the use of ophthalmic ointments are there

 Greasy nature
 The blurring of vision produced
 Imprecise dosing
 Difficult self-administration.

Blurring ‫ب‬ٙ‫ف ثظجج‬٠‫ؾض أٗ ِغ ػب‬١‫خ فج‬١ٕ٘‫ د‬ٝ‫ب ثزجم‬ٙٔ‫ق ال‬٠‫ب ِغ ِؾججٗ ٌٍّز‬ٙ‫ث‬ٛ١‫ٓ ثض ػ‬١‫ب ٌٍؼ‬ِٙ‫ ِّىٓ ٔظزخذ‬... ُ٘‫اٌّزا‬
ٌَٕٛ‫ً لجً ا‬١ٍ‫ٓ ث‬١‫ْ ثزىزت ِزاُ٘ اٌؼ‬ٛ١‫ ػؼبْ وذح ِؼظُ دوبرزح اٌؼ‬vision

ٍٝ‫ وفبءٖ اػ‬ٞ‫ذ‬١٘ ٌٟ‫ثبٌزب‬ٚ ‫ظخ‬٠ٛ‫عزٗ و‬ٚ‫ٓ ٔظزا الْ ٌش‬١‫ ِغ اٌؼ‬Contact time ‫د اي‬ٚ‫ش‬١‫ الٔٗ ث‬ٚ‫ٗ؟؟ ثزد‬١ٌ ِٗ‫مت ثظزخذ‬

ٓ١‫ب ٌٍؼ‬ِٙ‫ػ اطزخذ‬ّٛ‫اؽذح ِظ‬ٚ ٟٙٔ‫ ا‬Ointment base ‫ع ِٓ اي‬ٛٔ ‫ وذا‬ٞ‫مت ػٕذ‬

1) Hydrocarbon bases (oleaginous)

Yellow soft paraffin is preferred to white soft paraffin……??

 White soft paraffin is a bleached form of yellow soft paraffin, thereby being associated
with ocular irritancy

َ‫ ثض ثظزخذ‬Oleaginous base ‫ اي‬ٞ‫خ س‬١ٕ٘‫ ؽبعخ د‬ٟ‫ثخ ف‬ٚ‫خ فالسَ اد‬٠‫ اٌّب‬ٟ‫ثغ ف‬ٚ‫ذ‬١‫اء ِج‬ٚ‫ وبْ اٌذ‬ٌٛ Base ‫أب ثظزخذَ اي‬
‫ّخ‬ِٙ ‫؟؟‬White ‫ٗ ِجظزخذِغ اي‬١ٌ ‫ مت‬Yellow soft paraffin ‫اي‬

ِٗ‫ٕفؼغ اطزخذ‬١ِ ٌٟ‫ثبٌزب‬ٚ ٓ١‫ظ ٌٍؼ‬١ٙ‫ؼًّ ر‬١٘ ٗ‫ اطزخذِز‬ٌٛ ٖ‫د‬ٚ ‫ق‬١‫ٌٗ رج‬ّٛ‫ ثض ِؼ‬yellow ٓ‫ ػجبرح اؿال ػ‬ٛ٘ White ‫اي‬

2. Absorption base

‫خ‬١ٕ٘‫رح د‬ٛ‫ ؿ‬ٟ‫شٖ ف‬٠‫ػب‬ٚ ‫خ‬٠‫خ ِب‬٠ٛ‫ ػ‬ٟ‫ثٗ ف‬ٚ‫اء ٘ؾزبط اد‬ٚ‫ اٌذ‬ٍٛ‫ ف‬ٞ‫خ ػبد‬٠‫خ ِب‬٠ٛ‫ فبرذ ثض ثزمذر ربخذ ػ‬ٌٍٟ‫ ا‬ٞ‫ س‬ٞ‫اٌمبػذح د‬
ٞ‫٘خزبر اٌمبػذح د‬

3. Water-soluble bases/aqueous gels

Water-soluble bases (PEG) associated with a lower incidence of blurred vision (due to their
water-miscibility).

Lecture 4 & 5 Page | 9

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

Advantages: Gels have increased residence time and enhanced bioavailability than eye
drops.

ٞ‫ٗ ٘خزبر اٌمبػذح د‬١‫ثٗ ف‬ٚ‫ش اد‬٠‫ػب‬ٚ ‫خ‬٠‫ؾت اٌّب‬١‫اء ث‬ٚ‫ اٌذ‬ٌٛ ٝ‫ ٕ٘ب ثم‬... ‫خ‬٠ٛ‫ب ػ‬ِٕٙ ً‫ً ثض ارم‬١‫ ػجٗ اٌغ‬ٝ‫ ثم‬ٞ‫زح د‬١‫اٌمبػذح االخ‬
ٖ‫خ د‬٠‫ع ػذَ اٌزؤ‬ٛ‫ك‬ِٛ ً‫م‬١ٙ٘ ‫خ فّغ‬١ٕ٘‫ اٌذ‬ٟ‫ٕ٘ب ػؼبْ الً ف‬ٚ

N.B. Emulsion bases should not be used in the eye owing to ocular irritation produced by the
soaps and surfactants used to form the Emulsion.

ٓ١‫ظ ٌٍؼ‬١ٙ‫ ثزؼًّ ر‬ٚ‫ٗ؟؟ ػؼبْ ثزد‬١ٌ ‫ مت‬Emulsion base ‫ اي‬ٟ٘ ٓ١‫ب ٌٍؼ‬ِٙ‫ ِمذرع اطزخذ‬ٌٍٟ‫ ا‬Base ‫ اْ اي‬... ‫ّخ عذااا‬ِٙ

)Emulsion base ‫اي‬ٚ White paraffin( ‫ٓ عذااا‬١ِّٙ ‫ّغ‬ِٙ‫ٓ ِجظزخذ‬١‫ ؽبعز‬ٞ‫ وذح ػٕذ‬ٝ‫جم‬٠

Emulsion

 Prepared by: dispersing the active ingredient(s) into an oil phase, adding suitable
emulsifying and suspending agents and mixing with water vigorously to form a uniform
oil-in-water emulsion.

 Each phase is typically sterilized prior to or during charging into the mixing vessel.

 High-shear homogenation employed to reduce oil droplet size to sub-micron size which
may improve the physical stability of the oil micelles so they do not coalesce. The
resulting dosage form should contain small oil droplets, uniformly suspended.

Limited aqueous solubility of the drug substance(s) is the most common rationale for
developing an ophthalmic emulsion.

The drug substance(s) can be added to the phase in which it is soluble at the beginning of the
manufacturing process

ُ٘‫ثٕؾن ِؼب‬ٚ Oil ٟٔ‫اٌزب‬ٚ Water ُِٕٙ ‫اؽذ‬ٚ 2phase ‫ػزفٕب أٗ ػجبرح‬ٚ ‫ فبد‬ٌٍٟ‫ اٌززَ ا‬Emulsion ‫مجؼب اخذٔب اي‬
‫خ‬١‫د اٌضجبر‬ٚ‫ش‬٠ٚ ‫ ثؼق‬ٟ‫ا ف‬ٛ‫ث‬ٚ‫ذ‬٠ ْ‫ ػؼب‬Emulsifying agent

ٚ‫ُ ثجؼق ا‬ٙ‫رخٍط‬ٚ ٖ‫ؽذ‬ٌٛ ‫ذ‬٠‫اٌش‬ٚ ‫ؽذ٘ب‬ٌٛ ‫خ‬٠‫ ِّىٓ رؼمُ اٌّب‬.... ٓ١‫ اٌؼ‬ٟ‫ظزخذَ ف‬١٘ ٟ‫ائ‬ٚ‫ ػىً د‬ٞ‫ ا‬ٞ‫ْ ِؼمُ س‬ٛ‫ى‬٠ َ‫مجؼب الس‬
‫ االخز‬ٟ‫ُ ف‬ٙ‫ٓ رخٍط‬٠‫ثؼذ‬ٚ ٞ‫ ػبد‬Emulsion ‫ْ اي‬ٛ‫رى‬

‫ أب‬ٝ‫جم‬٠ )Hydrophilic( ‫خ‬٠‫ؾت اٌّب‬١‫اء ث‬ٚ‫ اٌذ‬ٌٛ ٟٕ‫ؼ‬٠ ‫ب‬ٙ‫ؾج‬١‫ ث‬ٌٍٟ‫ ا‬phase ‫ اي‬ٟ‫ٖ ف‬ٛ‫ث‬ٚ‫ذ‬٠ٚ ‫اء‬ٚ‫ا اٌذ‬ٛ‫ج‬١‫غ‬١‫ُ ث‬ٙٔ‫ ا‬ٝ‫ٌه ثم‬ٛ‫م‬١‫ث‬
Emulsion ‫ْ اي‬ٛ‫ٓ او‬٠‫ثؼذ‬ٚ ‫خ‬٠‫ اٌّب‬ٟ‫ثٗ ف‬ٚ‫٘ذ‬

Lecture 4 & 5 Page | 10

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

‫ ثزبػٗ اي‬Droplet ‫ئبد اي‬٠‫مًٍ ؽغُ عش‬١‫بس ث‬ٙ‫ دٖ ع‬Homogenizer ‫بس اي‬ٙ‫ ثذخٍٗ رؾذ ع‬Emulsion ‫لبٌه اي‬
Emulsion ‫خ اي‬١‫ صجبر‬ٟ‫ظبػذ ف‬١‫وّبْ ث‬ٚ ِٗ‫ظزخذ‬١‫ ث‬ٛ٘ٚ ‫ق‬٠‫غ اٌّز‬١‫م‬٠‫ٗ؟؟ لبٌه ػؼبْ ِلب‬١ٌ ‫ مت‬Emulsion

Emulsions may exhibit three types of instability:

 Flocculation, creaming, and coalescence.

To prevent flocculation, creaming and coalescence of the emulsions, manufacturers add

surfactants to increase the kinetic stability of the emulsion so that the emulsion does not change
significantly with time.

‫أب‬ٚ ‫ ثؼق‬ٟ‫ع ف‬ٛ‫ث‬ٚ‫ذ‬١‫ٗ اؿال ِج‬٠‫اٌّب‬ٚ ‫ذ‬٠‫ اخذٔبُ٘ لجً وذح اْ اٌش‬... Emulsion ‫ ِّىٓ رٕزظ ِٓ اي‬ٌٍٟ‫ٗ اٌّؼبوً ا‬٠‫مت ا‬
ٞ‫د‬ٚ Flocculation ْٛ‫زى‬٠ٚ ‫ا‬ٍٛ‫فـ‬٠ 2 phase ‫ٕٗ اي‬١‫ف ِؼ‬ٚ‫ ظز‬ٞ‫ا لبٌه ثض ِّىٓ رؾذ ا‬ٛ‫ث‬ٚ‫ذ‬٠ ْ‫ ػؼب‬EA َ‫ثظزخذ‬
‫ب‬ِٙ‫ غٍن اطزخذ‬ٞ‫مجؼب د‬ٚ Emulsion ‫ ططؼ اي‬ٍٝ‫رطٍغ ػ‬ٚ ‫ رزغّغ ِغ ثؼق‬Internal phase ‫ئبد اي‬٠‫ب اْ عش‬ٙ١‫ؾـً ف‬١‫ث‬
‫ئبد‬٠‫ اٌغش‬Creaming ‫اي‬ٚ ... ‫ذ‬٠‫ش‬٠ ‫ب‬ّٙ‫ؽغ‬ٚ ‫ب‬ٙ‫ ثؼل‬ٟ‫ئبد رٍشق ف‬٠‫ ػجبرح ػٓ اٌغش‬ٞ‫د‬ٚ coalescence ً‫ؾـ‬٠ ٚ‫ ا‬...
‫ اي‬ٚ‫ ا‬EA ‫د اي‬ٛ‫ع‬ٚ ‫ب‬ٙ‫ّٕؼ‬١‫ ث‬ٌٍٟ‫ا‬ٚ ً‫ ِؼبو‬ٞ‫ مجؼب وً د‬.... ‫ رززطت رؾذ‬ٚ‫ اٌظطؼ ا‬ٍٝ‫رطٍغ ػ‬ٚ ‫ ػىً مجمبد‬ٟ‫ثززغّغ ف‬
SAA

Strips

Ophthalmic strips are made of filter paper and are individually packed to ensure sterility until
the time of use.

‫ ثززؾلز وً عزػخ‬Filter paper ‫مخ وذح ػجخ اي‬١‫ ػجبرح ػٓ ؽبعخ رل‬ٞ‫ د‬Strip ‫اي‬
ٖ‫د‬ٚ ‫ؽذ٘ب‬ٌٛ ٗ‫ ِغٍم‬ٝ‫ب ثزجم‬ِٕٙ ‫ دٖ وً عزػخ‬... ‫ب ال‬ِٕٙ ‫ثزبخذ‬ٚ packet ‫ؽذ٘ب ِغ ِضال‬ٌٛ
‫ة‬ٚ‫ىز‬١ِ ٞ‫ ِؼزف ال‬ٝ‫جم‬١٘ ٟ‫اؽذٖ اٌجبل‬ٚ ‫ ثبوذ ٘زفزؼ‬ٌٛ ‫ب‬ٙٔ‫ ال‬Sterile ‫ب‬ٙٔ‫ػؼبْ رزأوذ ا‬

 Used in the measurement of tear production in dry eye

conditions. In this case, they are gauged for easy reading of the
measurement.

ٞ‫ ِٓ اٌذاخً س‬ٍٟ‫ٓ اٌظف‬١‫ عفٓ اٌؼ‬ٍٝ‫ثززؾن ػ‬ٚ ٓ١‫ اٌؼ‬ٟ‫ْ ف‬ٛ‫ ثززى‬ٌٍٟ‫ع ا‬ِٛ‫خ اٌذ‬١ّ‫ض و‬١‫ب ِّىٓ رظزخذَ ػؼبْ رم‬ِٙ‫اطزخذ‬
ٓ١‫ب اٌؼ‬ٙ‫ ثزطٍؼ‬ٌٍٟ‫ ا‬Tears ‫خ اي‬١ّ‫ب و‬ٌٙ‫زؾن ِؼب٘ب ؽبعخ ِذرعخ وذح ثؼزف ِٓ خال‬١‫ ث‬... ‫رح وذح‬ٛ‫اٌـ‬

Lecture 4 & 5 Page | 11

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

 Impregnated with certain drugs such as fluorescein sodium (used as diagnostic strips to
visualize defects or aberrations in the corneal epithelium by staining the areas of cellular
loss; to evaluate hard contact lens fitting and to evaluate applanation tonometry.

ٛ٘ٚ‫ر‬ٛ‫ٓ ػؼبْ اٌذوز‬١‫ٓ ثزـجغ اٌطجمبد ثزبػخ اٌؼ‬١‫ ططظ اٌؼ‬ٍٝ‫ب ػ‬ِٙ‫ب ؿجغخ ػؼبْ ٌّب اطزخذ‬ٙ١‫زؾن ف‬١‫ ث‬... ‫ب‬ِٕٙ ‫ع‬ٛٔ ٟٔ‫رب‬
‫ذا‬٠‫ب رؾذ‬ٙٔ‫ؼزف ِىب‬٠ ٓ١‫دح داخً اٌؼ‬ٛ‫ع‬ِٛ ‫ٗ ِؼىٍخ‬١‫ ف‬ٌٛ ‫ؼزف‬٠ ‫مذر‬٠ ‫فؾؾ‬١‫ث‬

Ocular inserts:

Ophthalmic inserts are solid dosage forms of appropriate size

and shape that are placed in the conjunctival fornix, in the
lachrymal punctum or on the cornea.

Drug release from soluble inserts involves two steps:

1. Fast release of apportion of the drug as the tear fluid

penetrates into the system
2. Slow release as a gel layer is formed on the surface of the
insert.

As the initial dissolution step is usually fast, the solubilized components can often cause blurred
vision.

Insert ‫ٗ اي‬١‫ أذ ؽبمن ف‬ٌٍٟ‫ اٌّىبْ ا‬ٟ‫اء ف‬ٚ‫ٓ ػؼبْ رطٍغ اٌذ‬١‫ اٌؼ‬ٟ‫ب ف‬ٍٙ‫اء ثزذخ‬ٚ‫ب اٌذ‬ٙ١‫ْ ف‬ٛ‫زى‬١‫ ث‬Solid ‫ ػجبرح ػٓ ؽبعخ‬ٞ‫د‬

‫ ططظ‬ٍٝ‫ة ػ‬ٚ‫ذ‬٠ Free ‫عشء‬ٚ polymer ٟ‫ت ف‬٠‫ اء دا‬ٚ‫ عشء ِٓ اٌذ‬... ‫اء‬ٚ‫ب اٌذ‬ٙ١ٍ‫ً ػ‬٠‫ػب‬ٚ polymer ‫ ػجبرح‬ٞ‫ د‬Insert ‫اي‬
polymer ‫اي‬

‫ز‬١‫ رأص‬ٞ‫رذ‬ٚ ‫اء‬ٚ‫ ِٓ اٌذ‬Free ‫ربخذ اٌغشء اي‬ٚ ‫ب‬ٙ١‫ع رخزٍن ث‬ِٛ‫ٓ اٌذ‬١‫ اٌؼ‬ٟ‫ب ف‬ٙ‫؟؟ لبٌه ِغزد ِب ثؾط‬ٞ‫ب اسا‬ِٕٙ ‫طٍغ‬١‫اء ث‬ٚ‫اٌذ‬
polymer ‫ اي‬ٟ‫ وبْ ف‬ٌٍٟ‫اء ا‬ٚ‫ً ِؼبٖ فبٌذ‬١‫ْ ع‬ٛ‫ب رى‬ٙ١‫رخزٍن ث‬ٚ ٗ‫ ٔفظ‬polymer ‫ اي‬ٍٝ‫ػ ػ‬ٚ‫ع ٘زز‬ِٛ‫ٓ اٌذ‬٠‫ثؼذ‬ٚ .... ‫غ‬٠‫طز‬
‫ع ِضال‬ٛ‫ٍخ رـً الطج‬٠ٛ‫ز ٌّذٖ م‬١‫ رأص‬ٞ‫ذ‬١‫ع دٖ ث‬ٌٕٛ‫ ا‬ٌٟ‫ثبٌزب‬ٚ Slow release ‫خزط ثض ة‬١٘ ٗ‫ٔفظ‬

Advantages

• Increased ocular residence, hence a prolonged drug activity and a higher bioavailability
• Better patient compliance, resulting from a reduced frequency of administration
‫ٍخ‬٠ٛ‫ز ِّزذ ٌفززح م‬١‫ رأص‬ٞ‫ب اؿال ػؼبْ رذ‬ِٙ‫ٌٕب أب ثظزخذ‬ٛ‫ ِب ل‬ٞ‫ب س‬ٙ‫شار‬١ِّ ‫مجؼب‬

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Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

‫ ػىض اٌمطزاد ِضال ثزؾزبط رىزار‬ٍٝ‫ز ػ‬١‫ رأص‬ٞ‫ع رذ‬ٛ‫اؽذح ٌّذح اطج‬ٚ ‫بخذ٘ب ِزح‬١٘ ‫ب‬ٙٔ‫ق ال‬٠‫ؾخ ٌٍّز‬٠‫ِز‬ٚ ‫ْ ِٕبطجخ‬ٛ‫ثزى‬
‫َ وذا عزػخ‬ٛ٠ ً‫اٌغزػخ و‬

Disadvantages:

• Their movement around the eye

• The occasional loss during sleep or while rubbing the eyes
• Their interference with vision
• Difficult placement of the ocular inserts
• Solidity, i.e., they are felt by patients as an extraneous body in the eye.
• Expensive
‫ ؽبعجخ‬ٚ‫جٗ ا‬٠‫ف ؽبعخ غز‬٠‫ق اؽظبص ثؼذَ اٌزاؽٗ ؽبطظٗ أٗ ػب‬٠‫ ٌٍّز‬ٞ‫ ٘زذ‬ٌٟ‫ثبٌزب‬ٚ Solid ‫ب‬ٙٔ‫ي ؽبعخ ا‬ٚ‫ ا‬... ٝ‫ب ثم‬ٙ‫ث‬ٛ١‫ػ‬
‫خ‬٠‫اٌزؤ‬

‫خ‬٠‫ِّىٓ رزذاخً ِغ اٌزؤ‬ٚ ‫ فمذ اٌغزػخ‬ٌٟ‫ثبٌزب‬ٚ ٕٗ١‫ب رمغ ِٓ ػ‬ٙ١ٍ‫ِّىٓ اٌؾزوخ رخ‬ٚ ٗ‫ رزؾزن ِغ صبثز‬ٞ‫ د‬Solid ‫ِّىٓ اي‬ٚ

‫خ‬١ٌ‫وّبْ غب‬ٚ ٗ‫ب ثٕفظ‬ِٙ‫ظزخذ‬٠ ‫ق‬٠‫مجؼب ؿؼت اٌّز‬

‫ثغ‬ٚ‫ذ‬١ِ ٓ‫ِّى‬ٚ ٓ١‫ طبئً اٌؼ‬ٟ‫ة ف‬ٚ‫ذ‬١‫ْ ث‬ٛ‫ى‬٠ ٓ‫ ِّى‬... ‫اء‬ٚ‫ً اٌذ‬٠‫ ػب‬ٌٍٟ‫ ا‬polymer ‫ ؽظت اي‬ٍٝ‫ٓ ػ‬١‫ػ‬ٛٔ ‫ب‬ِٕٙ ٗ١‫ف‬

They can be classified as erodible (soluble) and non-erodible (insoluble).

I. Insoluble inserts

• The Ocusert therapeutic system is a flat, flexible, elliptical device

• Designed to be placed in the inferior cul-de-sac between the sclera and the eyelid

• To release Pilocarpine continuously at a steady rate for 7 days.

‫ اي‬ٟ‫ت ف‬٠‫ دا‬ٌٍٟ‫اٌغشء ا‬ٚ ‫اء مت‬ٚ‫ ِٓ اٌذ‬Free ‫ع ثزخزٍن ثبٌغشء اي‬ِٛ‫ اٌذ‬ٟ‫ب ٘زالل‬ٙ‫ ِغزد ِب رؾط‬insert ‫اؽٕب ارفمٕب اْ اي‬
‫خزط‬٠ ‫ ِب‬ٍٝ‫ٍخ عذاا ػ‬٠ٛ‫فلً فززح م‬١٘ Insoluble ‫ثغ‬ٚ‫ذ‬١‫ ؽبٌخ أٗ ِج‬ٟ‫ ف‬polymer ‫ اي‬ٝ‫ ؽظت ثم‬ٍٝ‫ لبٌه ػ‬polymer
‫ع دٖ أذ ِؾزبط رزذخً ػؼبْ رطٍغ اي‬ٌٕٛ‫ٗ؟؟ لبٌه ا‬٠‫ؾـٍٗ ا‬١٘ ٖ‫ د‬polymer ‫ثؼذ ِب رخٍؾ اٌغزػخ اي‬ٚ ‫اء مت‬ٚ‫اٌذ‬
ٖ‫ د‬polymer

II. Soluble Ocular inserts:

Lecture 4 & 5 Page | 13

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

Advantage:

 Soluble so that they do not need to be removed from their site of application

)‫ّخ عذااأ‬ِٙ( ٓ١‫اء داخً اٌؼ‬ٚ‫ة ِغ اٌذ‬ٚ‫ذ‬١٘ ‫ الٔٗ اؿال‬polymer ‫اخزط اي‬ٚ ً‫ ارذخ‬ٟٔ‫ ِغ ِؾزبط ا‬ٝ‫ع دٖ ثم‬ٌٕٛ‫ا‬

Contact lenses

Contact lenses can be a way of providing extended release of drugs into the eye.

Conventional hydrogel soft contact lenses have the ability to absorb some drugs and release
them into the post lens lacrimal fluid, minimizing clearance.

ٟ‫ب ف‬ٍٙ‫ادخ‬ٚ ٟ‫اء ثزبػ‬ٚ‫ب اٌذ‬ٙ١ٍ‫أب ثؾلز٘ب ثؾًّ ػ‬ٚ ٓ١‫ ِؼ‬polymer ِٓ ْٛ‫ اٌؼذطبد اٌالؿمخ ثززى‬ٚ‫ ا‬Contact lenses ‫اي‬
‫اء‬ٚ‫ؾـً فمذ ٌٍذ‬١٘ ‫ ِغ‬ٌٟ‫ثبٌزب‬ٚ ‫ض‬٠ٛ‫ و‬ٞ‫ اٌؼذطبد د‬ٟ‫فـً ِبطه ف‬١‫اء ث‬ٚ‫ ٕ٘ب اٌذ‬... ٞ‫ٓ ػبد‬١‫اٌؼ‬

Intraocular Injections

 It is a shot of medicine into the eye.

 The inside of the eye is filled with a jelly-like fluid (vitreous).

 The medicine is injected into the vitreous.

 FDA approved intraocular injection of meiotic, corticosteroids, antivirals…..

ٓ١‫اؽذح داخً اٌؼ‬ٚ ‫ وطٍمخ‬ٟٕ‫ؼ‬٠ in shot ً‫ذخ‬١‫اء ث‬ٚ‫ي اْ اٌذ‬ٛ‫م‬١‫ٕب ث‬ٙ‫ٓ ف‬١‫اء داخً اٌؼ‬ٚ‫ ٘ؾمٓ اٌذ‬ٞ‫مخ د‬٠‫اٌطز‬

ٖ‫ش د‬١‫ٓ ثبٌززو‬١‫ؿً ٌٍؼ‬ٚ ٗٔ‫ارأوذ ا‬ٚ ٓ١‫ش ِؼ‬١‫اء ثززو‬ٚ‫ ٌّب اؽزبط ادخً د‬ٞ‫مخ د‬٠‫ثظزخذَ اٌطز‬

Intravitreal implant

This sterile implant is surgically implanted in vitreous cavity to release drug for 5-8 months.

 Employed to extend the release of drugs in ocular fluids and tissues particularly into the
posterior segment

ٕٗ‫ اخذٖ أب ثؾم‬ٟ‫اع‬ٚ ً١‫ ػىً ع‬ٍٝ‫اء ثزا ػ‬ٚ‫ت ِغ اٌذ‬٠‫ دا‬polymer ‫ ثض اٌفىزح ٕ٘ب اْ اي‬... Inserts ‫ فىزح اي‬ٞ‫ ػبٍِخ س‬ٞ‫د‬
‫ر‬ٛٙ‫ٍخ عذاا رـً ٌؼ‬٠ٛ‫مؼذ فززح م‬١‫شٖ ٕ٘ب أٗ ث‬١ٌّ‫ا‬ٚ ٓ١‫اء داخً اٌؼ‬ٚ‫طٍغ اٌذ‬٠ٚ ٓ١‫ذخً اٌؼ‬٠ ً١‫ اٌغ‬... ٓ١‫اؽمٕٗ داخً اٌؼ‬ٚ

ًّ‫ٔبد ِٕغ اٌؾ‬ِٛ‫ ثزخزط ٘ز‬ٌٍٟ‫ ثززؾن رؾذ اٌغٍذ ا‬ٌٍٟ‫ فىزح االثز ا‬ٞ‫ س‬ٞ‫د‬

Lecture 4 & 5 Page | 14

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

Implants can be broadly classified into two categories based on their degradation
properties:

1. Biodegradable

‫ٌخ‬ٛٙ‫ب ِٓ اٌغظُ ثظ‬ٙ‫خزع‬٠ ‫مذر‬٠ ُ‫اٌغظ‬

2. Non- Biodegradable

ٗ‫السَ رذخً ػؼبْ رخزع‬ٚ ‫د‬ٛ‫ع‬ِٛ ً‫فل‬١٘ٚ ‫ ثض‬polymer ‫خزط ِٓ اي‬١٘ ‫اء‬ٚ‫اٌذ‬

Iontophoresis

Iontophoresis is the process in which direct current drives ions into cells or tissues.

If the drug molecules carry a positive charge, they are driven into the tissues at the anode; if
negatively charged, at the cathode.

Advantages: fast, painless, safe, and results in the delivery of a high concentration of the drug
to a specific site.

‫دح‬ٛ‫ع‬ِٛ ٌٍٟ‫اء ٌالٔظغخ ا‬ٚ‫ؿً اٌذ‬ٚ‫ ػؼبْ ا‬ٟ‫زث‬ٙ‫بر و‬١‫ ثظزخذَ ر‬ٟٔ‫ٕ٘ب اٌفىزح ا‬ٚ Iontophoresis ‫ ػجبرح ػٓ اي‬ٞ‫مخ د‬٠‫اٌطز‬
ٓ١‫فبٌؼ‬

‫اء‬ٚ‫ب اٌذ‬ٍٙ‫ؿ‬ٚ‫ش ا‬٠‫ ػب‬ٌٍٟ‫ٓ ا‬١‫ؿً ٌالٔظغخ ثزبػٗ اٌؼ‬ِٛ َٛ‫ ٘م‬... ‫عجخ‬ِٛ ٗ‫اء ػؾٕز‬ٚ‫ىٓ اٌذ‬١ٌٚ ‫اء‬ٚ‫ٗ اٌذ‬١‫ ف‬ٌٍٟ‫ي ا‬ٍٛ‫اٌفىزح اْ اٌّؾ‬
‫اء‬ٚ‫ اٌذ‬ٌٟ‫ثبٌزب‬ٚ )‫ب‬ٙ١‫ؿٍٗ ث‬ِٛ ٌٍٟ‫د ا‬ٛٔ‫ػ ٌالٔظغخ (اال‬ٚ‫ز‬١٘ )‫عجخ‬ِٛ ٕٗ‫ٗ ػؾ‬١ٍ‫ ػ‬ٌٍٟ‫اء (ا‬ٚ‫ؼزغً اٌذ‬٠ ٟ‫زث‬ٙ‫بر اٌى‬١‫ٌّب اٌز‬ٚ ‫د‬ٛٔ‫ثأ‬
)‫د‬ٛ‫ب ثبٌىبص‬٠‫ؿً اٌخال‬ٛ٘( ‫اء ػؾٕزٗ طبٌجخ‬ٚ‫ اٌذ‬ٌٛ ... ‫ي‬ٛ‫ؿً ٌالٔظغخ ػٍط‬ٚ

‫اٌّىبْ اٌّؾذد‬ٚ ‫ؿً ٌالٔظغخ‬ٛ١‫اء ث‬ٚ‫ ِٓ اٌذ‬ٌٟ‫ش ػب‬١‫وّبْ رزو‬ٚ ٓ‫ اٌؾم‬ٞ‫بع أٌُ س‬ٙ‫ؼخ ِف‬٠‫ب طز‬ٙٔ‫ ا‬ٝ‫ ثم‬ٞ‫مخ د‬٠‫ اٌطز‬ٟ‫شح ف‬١ٌّ‫ا‬
ٗ‫ش اػبٌغ‬٠‫ أب ػب‬ٌٍٟ‫ا‬

Colloidal Systems

These dosage forms include liposomes, nanoparticles, microemulsions, nanoemulsions, etc.

A. Liposomes

Lecture 4 & 5 Page | 15

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

• Liposomes are lipid vesicles (Phospholipid) containing aqueous core and have been
widely exploited in ocular delivery for various drug substances.

• Depending on the nature of the lipid composition s elected, liposomes can provide
extended release of the drug.

• Disadvantages: high cost and the variable purity of phospholipids.

B. Niosomes

• Structurally niosomes are similar to liposomes, in that they are bilayer. However, the
bilayer in the case of niosomes is made up of nonionic surface-active agents rather than
phospholipids as in the case of liposomes.

ً‫اء داخ‬ٚ‫ب اٌذ‬ٙ١‫ ثمذر ادخً ف‬ٌٍٟ‫ ِٓ اٌطزق ا‬ٞ‫ د‬Liposomes ‫ُ اي‬ِٕٙ ‫ع‬ٛٔ ‫ي‬ٚ‫ف ا‬ٛ‫ ٕ٘ؼ‬.... Colloidal systmes ٗ١‫ف‬
ً‫ٓ اٌؼى‬٠‫اخذ‬ٚ ْٛ٘‫ٓ ِٓ اٌذ‬١‫ مجمز‬phospholipid by layer ٓ‫ب ػجبرح ػ‬ٙٔ‫ب ا‬ٙ‫ٓ فىزر‬١‫اٌؼ‬
‫ أب‬ٌٟ‫ثبٌزب‬ٚ SAA ‫ْ ِغ‬ٛ٘‫ٓ د‬٠ٛ‫) ثض ٕ٘ب اٌزى‬Micelle ‫ فىزح اي‬ٞ‫ لذاِه دٖ (ػبٍِٗ س‬ٌٍٟ‫ا‬
ٌٛ ‫ أّب‬liposome ًٌ ٍٟ‫ اٌغشء اٌذاخ‬inside core ٍٗ‫خ ٘ذخ‬٠‫ اٌّب‬ٟ‫ة ف‬ٚ‫ذ‬١‫اء ث‬ٚ‫ب د‬٠‫ ِؼب‬ٌٛ
‫ثؼذ‬ٚ Core ‫ذٖ ػٓ اي‬١‫ْ ثؼ‬ٛ‫رى‬ٚ lipid ‫خ ٘ذخٍٗ داخً مجمبد اي‬٠‫ اٌّب‬ٟ‫ثغ ف‬ٚ‫ذ‬١‫اء ِج‬ٚ‫ب د‬٠‫ِؼب‬
ِٓ ‫اء‬ٚ‫رخزط اٌذ‬ٚ ٗ‫ب فجزذخً ثظزػٗ داخً االٔظغ‬٠‫ْ ػجٗ اٌخال‬ٛ‫ ثزى‬ٞ‫ د‬Liposomes ‫وذح اي‬
‫ فّغ‬Rancidity ‫ب‬ٍٙ‫ؾـ‬٠ ‫رشرٔخ‬ٚ ‫ ِّىٓ رزأوظذ‬ٞ‫ْ د‬ٛ٘‫وّبْ اٌذ‬ٚ ‫خ عذااا‬١ٌ‫ْ غب‬ٛ‫ب ثزى‬ٙٔ‫ب ا‬ٙ‫ ِؼىٍز‬.... ‫ز‬١‫ اٌزأص‬ٞ‫رذ‬ٚ ‫ا٘ب‬ٛ‫ع‬
Niosome ‫ اي‬ٟٔ‫ع اٌزب‬ٌٕٛ‫ا ا‬ٍّٛ‫ ٌٍغظُ ػؼبْ وذح ػ‬pure ٝ‫٘زجم‬

SAA ‫ب ِٓ اي‬ٙٔٛ‫ْ ال أب ثى‬ٛ٘‫ْ ِٓ د‬ٛ‫ٔفض اٌؼىً ثض ثذي ِب ثززى‬ٚ ‫ ثبٌظجن‬Liposomes ‫ ٔفض فىزح اي‬Niosomes ‫اي‬
Liposomes ‫ اي‬ٟ‫ب ف‬ٙ١‫ وٕذ ثالل‬ٌٍٟ‫ؾـٍغ اٌّؼبوً ا‬١ِٚ ‫خ‬١‫د اٌضجبر‬ٚ‫ػؼبْ اس‬

C. Nanosuspensions
• Nanosuspensions can be defined as sub-micron colloidal systems that consist of poorly
water soluble drug, suspended in an appropriate dispersion medium stabilized by
surfactants.

• They help in enhancement of drug solubility and thus bioavailability.

Lecture 4 & 5 Page | 16

Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

• Unlike microemulsions, they are non-irritant. Charge on the surface of nanoparticles

facilitates their adhesion to the cornea.

ٓ١‫زح داخً اٌؼ‬١‫ئبد وج‬٠‫ٕفؼغ اطزخذَ عش‬١ِ ‫ أب‬Suspension ‫ اي‬ٟ‫ٌٕبٖ ف‬ٛ‫ ل‬ٌٍٟ‫دٖ ٔفض اٌىالَ ا‬ٚ Nanosuspensions ‫اي‬
ٓ١‫ اٌؼ‬ٟ‫ْ ػؼبْ ِزغزؽغ ف‬ٚ‫ىز‬١ِ 03 ِٓ ً‫زٖ ال‬١‫ْ ؿغ‬ٛ‫السَ رى‬

ُ‫ز‬١‫ ث‬ٞ‫د‬ٚ Sonicators ‫ ِضال اي‬ٞ‫شح س‬ٙ‫ك اع‬٠‫ ػٓ مز‬ٛٔ‫ؿً ٌٍٕب‬ٛ‫ئبد اؿغز ثز‬٠‫ ٌغش‬Suspension ‫ي اي‬ٛ‫ٕ٘ب أب ثؾ‬
‫ال ال‬ٚ ‫ف دٖ اٌؾغُ اٌّؾذد فؼال‬ٛ‫ٔؼ‬ٚ ‫ب اخزجبراد‬ٍّٙ‫زؼ‬٠ َ‫الس‬ٚ ‫زح‬١‫ثّزاؽً وز‬

ٖ‫ اٌغشء د‬ٟ‫اْ ف‬ٕٛ‫ف اخز ػ‬ٛ‫ٓ ٕ٘ؼ‬١‫ؿً ٌٍؼ‬ٛ١‫اء ث‬ٚ‫ب اٌذ‬ٌٙ‫ ِٓ خال‬ٌٍٟ‫وذح خٍـٕب اٌطزق ا‬

CONTAINER/ CLOSURE SYSTEMS

Traditionally, ophthalmic liquid products were packed in glass containers fitted with an eye
dropper.
Today, glass containers have limited use where product stability or compatibility issues exclude
the use of flexible plastic containers made of polyethylene or polypropylene.
Most liquid ophthalmic products on the market are packaged in plastic containers fitted
with nozzles from which, by gentle squeezing, the contents may be delivered as drops.
 Minimizing the risk of the contents being contaminated with microorganisms
Also, plastic containers are cheap, light in weight, more robust to handle and easier to use than
glass-dropper type containers.
Disadvantages of plastic container
 Some plastic materials such as polyethylene can absorb some antimicrobial preservatives
(e.g. Benzalkonium chloride), or some drugs.
 Leach plasticizers into the product, or printing inks from the label can migrate through
the plastic into the product.
‫ب وذا‬ٙ١‫ ف‬ٝ‫جم‬١‫ ث‬Glass container ‫ا اي‬ِٛ‫ظزخذ‬١‫ا ث‬ٛٔ‫ سِبْ وب‬... ‫اء‬ٚ‫ٗ اٌذ‬١‫ ِّىٓ ٔؾن ف‬ٌٍٟ‫ ا‬Container ‫ٕ٘جذأ ٔزىٍُ ػٓ اي‬
ٓ‫ ٌى‬Sterile ‫ي عزػخ أذ ٘ززأوذ اْ اٌغزػخ‬ٚ‫٘ىذا فب‬ٚ ٗ‫خ رفزؾ‬١ٔ‫ٓ فبٌغزػٗ اٌزب‬٠‫ٓ ثزمفٍٗ ثؼذ‬٠‫ثؼذ‬ٚ ٗ‫عزػخ ثزفزؼ ربخذ اٌغزػ‬
Plastic container ‫ا اي‬ِٛ‫ظزخذ‬٠ ‫ا‬ٚ‫ ػؼبْ وذح ثذأ‬Sterility ‫ِزلّٕغ اي‬ٚ ‫ثبد‬ٚ‫ىز‬١ٌٍّ ‫ ِؼزف‬ٝ‫جم‬٠ ‫اداَ ارفزؼ‬
‫ة‬ٛ١‫ٗ ػ‬١‫ة ؟؟ لبٌه ال ف‬ٛ١‫بع ػ‬ٍِٙ ً٘ ‫ اٌلغن ثزخزط اٌغزػخ مت‬ٚ‫ ا‬Squeeze ‫ٗ فزؾبد وذح ِغ اي‬١‫ ف‬ٝ‫ٕ٘ب ثم‬

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Pharmaceutics IV Ocular (Dr / Eman 1) Amr FaYed & SalMa

ٗ‫اء ٔفظ‬ٚ‫وّبْ ِّىٓ رّزؾ اٌذ‬ٚ ‫ي‬ٍٛ‫اد اٌؾبفظخ ِٓ اٌّؾ‬ٌّٛ‫ ِّىٓ رّزؾ ا‬Plastic ‫ب اي‬ٙ١‫ ثٕـٕغ ث‬ٌٍٟ‫اد ا‬ٌّٛ‫ال ا‬ٚ‫ا‬
‫ي‬ٍٛ‫خغ اٌّؾ‬٠ٚ ‫ا‬ٚ‫زظزة ثزد‬٠ ‫ اٌشعبعخ‬ٍٝ‫د ػ‬ٛ‫ع‬ِٛ ٌٍٟ‫ِّىٓ اٌؾجز ا‬ٚ ‫ي‬ٍٛ‫ب ٌٍّؾ‬ٍٙ‫رذخ‬ٚ ‫ثخ ِٓ ثزا‬ٛ‫وّبْ ِّىٓ رظزة اٌزم‬
The challenge is to develop a packaging system for preservative-free products that
maintains the sterility of the product throughout its shelf-life and during use.
Sterility and Antimicrobial Preservative
A. Sterility:
 Ideally, all ophthalmic products would be terminally sterilized in the final packaging.
 Only a few ophthalmic drugs formulated in simple aqueous vehicles are stable to normal
autoclaving temperatures and times (121 oC for 20-30 min).
 Such heat-resistant drugs may be packaged in glass or other heat-deformation-resistant
packaging and thus can be sterilized this manner.
 Most ophthalmic products, however cannot be heat sterilized due to the active principle
or polymers used to increase viscosity are not stable to heat.
Aseptic ‫ْ ػٕذ٘ب ِىبْ اي‬ٛ‫ْ ِؼمّخ فالسَ اٌؼزوخ اٌّـٕؼٗ رى‬ٛ‫ب السَ رى‬ٙٔ‫ٓ ارفمٕب ا‬١‫ ٘زذخً اٌؼ‬Dosage form ٞ‫مجؼب ا‬
‫ك اٌؾزارح ثض‬٠‫ ػٓ مز‬Autoclave ‫زُ٘ اي‬ٙ‫زح عذاا اػ‬١‫ك مزق وز‬٠‫زُ ػٓ مز‬١‫ُ ث‬١‫ مجؼب اٌزؼم‬.... ُ‫ ِؼم‬ٛ٘ ٌٍٟ‫ ا‬area
Radiation ‫زىظز ِّىٓ ٔغزة ِؼبٖ اي‬١‫ ث‬ٌٛ ٓ‫زىظزع ثبٌؾزارح ٌى‬١‫ ِج‬product ‫ وبْ اي‬ٌٛ ‫ ِزٕفؼغ اال‬ٞ‫اٌطزلخ د‬
Preservatives are included in multiple-dose eye solutions for maintaining the product sterility
during use
• Preservatives not included in unit-dose package
• The use of preservatives is prohibited in ophthalmic products that are used at the of eye
surgery because if sufficient concentration of the preservative is contacted with the
corneal endothelium, the cells can become damaged causing clouding of the cornea and
possible loss of vision
So, these products should be packaged on sterile. unit-of-use containers .
The most common organism is Pseudomonas aeruginosa that row in the cornea and cause loss
of vision

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‫‪Pharmaceutics IV‬‬ ‫)‪Ocular (Dr / Eman 1‬‬ ‫‪Amr FaYed & SalMa‬‬

‫م‪١‬ت اي ‪ product‬مٍغ ِٓ اٌّـٕغ ِؼمُ ا‪ ٗ٠‬اٌٍ‪١٘ ٟ‬ؾبفع ػٍ‪ ٗ١‬أٗ ‪٠‬فلً ِؼمُ وذح ؟؟‬
‫لبٌه ف‪ ٟ‬ؽبٌخ ٌ‪ ٛ‬اي ‪ Container‬ف‪ ٗ١‬وذا عزػخ السَ رل‪١‬ف ِ‪ٛ‬اد ؽبفظخ مت ٌ‪ ٛ‬وبْ اي ‪ Container‬دٖ عزػخ ‪ٚ‬اؽذٖ‬
‫٘زظزخذَ ِغ ِؾزبط ٕ٘ب اك‪١‬ف ا‪ ٞ‬ؽبعخ الٔ‪ٙ‬ب ٘زظزخذَ ِزح ‪ٚ‬اؽذٖ ‪ٚ‬خالؽ‬
‫كدة خلصنا جسء ال ‪ Ocular‬وبالتوفيق ان شاء هللا‬

‫‪Lecture 4 & 5‬‬ ‫‪Page | 19‬‬